March 6, 2017
Augmenix reported results of a phase III trial of SpaceOAR System hydrogel for maintaining sexual function and potency following intensity modulated radiation therapy (IMRT) during prostate radiotherapy. Studies have shown a correlation between radiation dose to the penile bulb, a structure at the base of the penis, and post-radiotherapy impotence. In the SpaceOAR System trial, the median radiation dose to the penile bulb was reduced by 49% in SpaceOAR treated patients (21 Gy for Control vs. 11 Gy for SpaceOAR treated, p=0.036). Among men who were potent at baseline, the analysis showed that SpaceOAR treated men were better able to maintain erections sufficient for intercourse through three years of follow-up (p=0.03). Of the men treated with SpaceOAR, 66.7% were able to have erections sufficient for intercourse at three years compared to 37.5% in the Control arm, a 77.8% improvement.
February 27, 2017
OncoGenex Pharmaceuticals reported results of apatorsen in two randomized phase II clinical trials for bladder and prostate cancer. The Borealis-2 trial evaluated apatorsen in combination with docetaxel treatment in 200 patients with metastatic bladder cancer whose disease had progressed following first-line platinum-based chemotherapy. Patients who received apatorsen treatment experienced a 20% reduction in risk of death, compared to patients receiving docetaxel alone (overall survival hazard ratio (HR)=0.80; 80% CI: 0.65-0.98; p=0.078). Partial or complete responses occurred in 16.2% patients receiving apatorsen plus docetaxel compared to 10.9% patients receiving docetaxel alone with median response durations of 6.2 months versus 4.4 months, respectively. Higher baseline serum heat shock protein 27 (Hsp27) levels were significantly prognostic for indicating an almost two-fold higher risk of death (HR=1.96; p=0.0001). In an exploratory analysis on a subset of patients (20% of total) who completed at least two treatment cycles and had either a decrease in serum Hsp27 levels from baseline or had only a 20.5% increase in serum Hsp27 levels from baseline, the reduction in risk of death with apatorsen treatment was 71% (HR=0.29: 80% CI: 0.18-0.48; interaction p=0.0727). The Pacific trial evaluated the ability of apatorsen, when added to Zytiga (abiraterone acetate), to reverse or delay treatment resistance in 72 men who were experiencing a rising PSA on Zytiga alone. The primary endpoint evaluated the proportion of patients who were progression free (clinical and radiologic) at study day 60 with apatorsen added to Zytiga, compared to continuing Zytiga alone. In men receiving apatorsen, 33% were progression free at study day 60 compared to 17% for those men receiving Zytiga alone. For patients with five circulating tumor cells (CTCs) at baseline, 22% vs 11% of patients had a CTC reduction to less than five CTCs when apatorsen was added to Zytiga vs Zytiga alone, respectively. Clinical data from trials in bladder and prostate cancers demonstrated apatorsen was well-tolerated and improved patient outcomes when administered in combination with standard-of-care treatments.
February 6, 2017
Foresee Pharmaceuticals released results of a phase III trial of FP-001 LMIS (Leuprolide Mesylate Injectable Suspension) 50mg for advanced prostate carcinoma. In the study, 137 subjects were enrolled and received a minimum of one dose of the study drug (ITT population), and 124 subjects completed the study without major protocol violations that would affect the primary efficacy endpoint (per-protocol population (PP)). The 95% CI from Kaplan-Meier estimates was (92.2%, 98.9%), and the 95% repeated-confidence interval was (92.5%, 99.4%). By day 28, mean testosterone concentration was suppressed below castrate levels to 17.6ng/dL, and the suppression rate was 98.5% (135 out of 137 subjects achieved medical castration). No mean increase in testosterone was observed after the second injection. Four subjects did not achieve successful suppression of testosterone by the primary efficacy end point analysis, two of which failed to achieve castration level on day 28 and the other two had transient testosterone escapes. The most common adverse events reported in this study included hot flushing (48.9%), followed by hypertension (14.6%), injection site pain (7.3%), fatigue (6.6%), etc., most in mild or moderate intensity. Overall, treatment with LMIS 50mg injection every six months was safe and well-tolerated. The primary efficacy end point was achieved in 97% of subjects.
September 6, 2016
Nymox Pharmaceutical reported results of a phase III trial of fexapotide in late stage development for enlarged prostate (BPH) and for localized prostate cancer. Long-term outcomes were determined in 391 patients who were given double-blind placebo injections, which were followed by crossover to other treatments at the patients’ discretion. The numbers of blinded placebo patients who subsequently received surgical treatment during the next two to three years for their BPH symptoms were then prospectively analyzed. Results have now shown that there was an 82 to 95% reduction in the number of these patients who required surgery after they received crossover fexapotide in the trial, as compared to patients who did not receive fexapotide but instead received crossover, conventionally approved BPH treatments (p<0.0001).
March 28, 2016
Janssen-Cilag International issued phase III results of ZYTIGA (abiraterone acetate) plus prednisone for early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). COU-AA-302 was an international, randomized, double-blind, placebo-controlled study that included 1,088 men with mCRPC who had not received prior chemotherapy and were randomized to receive ZYTIGA (abiraterone acetate) 1,000 milligrams (mg) administered orally once-daily plus prednisone 5mg administered twice-daily or placebo plus prednisone 5mg administered twice-daily. The co-primary endpoints of the study were rPFS and OS. The post-hoc analysis used the final dataset for the intent-to-treat population (n=1,088), to stratify patients into Group 1 (BPI 0-1, PSA <80 ng/ml and GS <8) and Group 2 (BPI=2 and/or PSA=80ng/ml and/or GS=8). The study provided an 11.8 months overall survival (OS) benefit (53.6 months vs. 41.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055), compared to an active control of placebo plus prednisone. The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostate-specific antigen [PSA] below 80ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055) (Group 2: 2.8 months; HR=0.84 [95% CI, 0.72-0.99]; p=0.0321).
January 18, 2016
Astellas US and Medivation released
results from the phase II TERRAIN trial of
enzalutamide compared to bicalutamide in
metastatic castration-resistant prostate cancer
(CRPC). The trial enrolled 375 patients in North
America and Europe, and evaluated enzalutamide
160mg once daily versus bicalutamide
50mg once daily. The TERRAIN study achieved
its primary endpoint demonstrating a statistically
significant increase in progression-free
survival (PFS) for enzalutamide compared to
bicalutamide (hazard ratio=0.44; 95% confidence
interval, 0.34-0.57; p<0.0001). Median
PFS, defined as time from randomization to
centrally confirmed radiographic progression,
skeletal-related event, initiation of new
anti-neoplastic therapy or death, whichever
occurred first, was 15.7 months in the enzalutamide
group compared to 5.8 months in the
bicalutamide group. The observed adverse
event profile of enzalutamide in TERRAIN
appeared consistent with that from phase
III enzalutamide trials. The median time on
treatment in TERRAIN was 11.7 months in the
enzalutamide group versus 5.8 months in the
bicalutamide group. Serious adverse events
were reported in 31.1% of enzalutamide-treated
patients and 23% of bicalutamide-treated
patients. Individual grade three or
higher adverse events largely occurred at a
similar rate (<1% difference) between treatment
groups, with the exception of hypertension
(7.1% v. 4.2%) and back pain (2.7% v.
1.6%), which occurred more frequently in the
enzalutamide treatment group. Grade three or
higher cardiac events were reported in 5.5%
of enzalutamide-treated patients versus 2.1%
of bicalutamide-treated patients. Two seizures
were reported in the enzalutamide group and
one in the bicalutamide group.
June 22, 2015
OncoGenex Pharmaceuticals released results of a phase III study of custirsen therapy in men with metastatic castrate-resistant prostate cancer (CRPC) who had a poor prognosis. The trial evaluated custirsen plus docetaxel/prednisone compared with docetaxel/prednisone alone in men with metastatic CRPC (n=1,022). Following 509 deaths, median overall survival (OS) was 23.4 months (m) v. 22.2 m for custirsen and control arms, respectively (hazard ratio [HR] 0.93; P = 0.42). Median survival for the poor and good prognosis groups in the control arm was 14 m and 30.4 m, respectively (HR = 3.66). The custirsen HR effect differed between poor and good prognosis groups (interaction P = 0.069). The HR estimate for custirsen survival benefit for those in the poor prognosis group was 0.73 (95% CI: 0.59 to 0.90) and 1.02 (95% CI: 0.76 to 1.37) for those in the good prognosis. When analyzed separately (n=492), the median OS in the poor prognostic group was 17 m in the custirsen arm v. 14 m in the control arm (HR=0.73, 95% CI: 0.59 to 0.90, P = 0.004).
March 30, 2015
Astellas Pharma and Medivation issued
results from a phase II study of enzalutamide
compared to bicalutamide in metastatic
castration-resistant prostate cancer (CRPC).
The phase II trial enrolled 375 patients in North
America and Europe and was designed to
evaluate enzalutamide at a dose of 160mg
taken orally once daily v. bicalutamide at a dose
of 50mg taken once daily. The median PFS in
the enzalutamide arm was 9.9 months longer
compared to that in the bicalutamide arm
(15.7 v. 5.8 months, respectively) with a Hazard
Ratio (HR) of 0.44 (95% confidence interval
[CI], 0.34-0.57; p<0.0001). The median time to
PSA progression was 13.6 months longer with
enzalutamide (19.4 months) relative to bicalutamide
treatment (5.8 months) with an HR of
0.28 (p<0.0001). 82% of enzalutamide-treated
patients achieved >= 50% PSA reduction from
baseline by week 13 v. 21% of bicalutamide-treated
patients. The median time on enzalutamide
treatment was 11.7 months compared
to 5.8 months on bicalutamide.
February 2, 2015
Medivation and Astellas Pharma reported
results of a phase II study comparing
enzalutamide with bicalutamide in men with
metastatic castration-resistant prostate cancer.
The phase II TERRAIN trial enrolled 375 patients
in North America and Europe. The trial involved
patients with metastatic prostate cancer whose
disease progressed despite treatment with a
luteinizing hormone-releasing hormone (LHRH)
analogue therapy or following surgical castration.
The trial was designed to evaluate enzalutamide
at a dose of 160mg taken once daily
v. bicalutamide at a dose of 50mg taken once
daily, the approved dose in combination with an
LHRH analogue. The study achieved its primary
endpoint demonstrating a statistically significant
increase in progression-free survival (PFS) for
enzalutamide compared to bicalutamide (Hazard
Ratio=0.44; 95% Confidence Interval, 0.34-
0.57; p<0.0001). Median PFS was 15.7 months
in the enzalutamide group compared to 5.8
months in the bicalutamide group. The median
time on treatment in TERRAIN was 11.7 months
in the enzalutamide group v. 5.8 months in the
bicalutamide group. Serious adverse events
were reported in 31.1% of enzalutamide-treated
patients and 23.3% of bicalutamide-treated patients.
Grade 3 or higher cardiac adverse events
were reported in 5.5% of enzalutamide-treated
patients v. 2.1% of bicalutamide-treated patients.
Two seizures were reported in the enzalutamide
group and one in the bicalutamide group. The
most common side effects occurring during
treatment and more common in the enzalutamide-
treated v. bicalutamide-treated patients
included fatigue, hot flush, hypertension, diarrhea,
weight decreased and pain in extremity.
October 13, 2014
Janssen R&D issued results of a phase
III study of ZYTIGA (abiraterone acetate)
plus prednisone in men with chemotherapynaive
metastatic castration-resistant prostate
cancer (mCRPC). The international, randomized,
double-blind, placebo-controlled study
included 1,088 men with mCRPC who had
not received prior chemotherapy and were
randomized to receive ZYTIGA (abiraterone
acetate) 1,000mg administered orally once
daily plus prednisone 5mg twice daily or
placebo plus prednisone 5mg twice daily. The
study demonstrated a 19% reduction in risk
of death in this study population (median OS,
34.7 v. 30.3 months, respectively; HR= 0.81
[95% CI, 0.70-0.93]; p = 0.0033), after a median
follow-up of more than four years (49.2
months). 67% of men in the ZYTIGA plus
prednisone arm and 80% in the control arm
received subsequent therapy. This includes
44% of men in the control arm who subsequently
received ZYTIGA plus prednisone.
The use of subsequent therapies did not impact
the statistical significance between the
ZYTIGA and control arms and makes these
results all the more compelling after adjusting
for the crossover effect. Final analysis
demonstrated a significant improvement in
median time to opiate use for cancer-related
pain compared to placebo plus prednisone
(median 33.4 v. 23.4 months, respectively;
HR= 0.72 [95% CI, 0.61-0.85]; p = 0.0001).
With two additional years (a total of four
years) of follow-up since the last clinical cutoff
(median 49.2 months), the safety profile
of ZYTIGA remained unchanged compared to
previous reports. Janssen has initiated regulatory
submissions to health authorities for a
revision to the ZYTIGA label.
February 17, 2014
Medivation and Astellas Pharma
released results of a phase III trial of
enzalutamide in patients with chemotherapy-
naïve metastatic prostate cancer who
have failed androgen deprivation therapy
and have few or no symptoms. The trial
is a randomized, double-blind, placebocontrolled,
multi-national trial that enrolled
more than 1,700 patients at sites in the U.S.,
Canada, Europe, Australia, Russia, Israel and
Asian countries including Japan. The trial
was designed to evaluate enzalutamide at
a dose of 160mg taken orally once daily v.
placebo. Treatment with enzalutamide demonstrated
a statistically significant overall
survival benefit compared with placebo
treatment. Enzalutamide reduced the risk
of death by 29% (HR=0.71). Treatment with
enzalutamide significantly reduced the
risk of radiographic progression or death
by 81% compared with placebo treatment
(HR=0.19). Men taking enzalutamide
experienced a 17-month delay in the time to
initiation of chemotherapy compared with
men taking placebo (28.0 months versus
10.8 months; HR=0.35). Enzalutamide extended
the median time to PSA progression
from 2.8 months (placebo) to 11.2 months
(HR= 0.169). Nearly four out of five patients
in the enzalutamide group experienced a
PSA decline of 50% or more, compared to
less than 4% in the placebo group (78% vs.
3.5%). Regulatory applications to the FDA
will be filed in early 2014.
November 11, 2013
Medivation and Astellas Pharma reported results of a phase III trial of enzalutamide in 1,700 men with metastatic prostate cancer that has progressed despite androgen deprivation therapy and who have not yet received chemotherapy. The randomized, double-blind, placebo-controlled, multinational trial enrolled patients at sites in the U.S., Canada, Europe, Australia, Russia, Israel and Asian countries including Japan. The trial was designed to evaluate enzalutamide at a dose of 160mg taken orally once daily v. placebo. Patients treated with enzalutamide demonstrated a statistically significant overall survival advantage compared with patients receiving placebo (p<0.0001). Enzalutamide provided a 30% reduction in risk of death compared with placebo (Hazard Ratio=0.70; 95% confidence interval, 0.59- 0.83). Patients treated with enzalutamide demonstrated a statistically significant radiographic progression-free survival advantage compared with placebo (p<0.0001). Enzalutamide provided an 81% reduction in risk of radiographic progression or death compared with placebo (Hazard Ratio=0.19; 95% confidence interval, 0.15-0.23). The percentage of patients alive in the enzalutamide arm was 72%, as compared with 65% in the placebo arm, at the time of the interim analysis data cut-off date. Treatment with enzalutamide resulted in a calculated point estimate for median overall survival of 32.4 months (95% confidence interval, 31.5 months-upper limit not yet reached) v. 30.2 months (95% confidence interval, 28.0 months-upper limit not yet reached) for patients receiving placebo. Medivation and Astellas will initiate meetings with and submissions to regulatory agencies beginning in early 2014.
July 29, 2013
Bayer HealthCare issued results from a phase III study of Xofigo in castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. The randomized, double-blind, placebo-controlled, international study enrolled 921 patients in 100 centers in 19 countries. Patients were stratified based on their baseline alkaline phosphatase (ALP) level, current bisphosphonate use and whether or not they had received docetaxel prior to enrollment. Treatment consisted of up to six intravenous injections separated by four weeks. Xofigo improved overall survival (OS) at the prespecified interim analysis (HR=0.695, [95% CI: 0.552-0.875], p=0.00185); median OS was 14.0 months with Xofigo (95% CI: 12.1-15.8) vs. 11.2 months with placebo (95% CI: 9.0-13.2). These findings were supported by an exploratory analysis performed before patient crossover with an additional 214 events in which Xofigo showed improvement in OS (HR=0.695, [95% CI: 0.581-0.832]); median OS was 14.9 months in the Xofigo arm (95% CI: 13.9-16.1) v. 11.3 months in the placebo arm (95% CI: 10.4-12.8). These data supported the FDA approval of Xofigo injection in May.
February 25, 2013
Progenics Pharmaceuticals released results from a phase I trial of PSMA ADC for prostate cancer. This open-label, dose-escalation study enrolled 52 men with metastatic castration-resistant prostate cancer that had progressed despite prior treatment with taxane-based chemotherapy regimens. Subjects received nine different dosing levels of PSMA ADC administered at three-week intervals for 12 weeks. Significant antitumor activity was observed across doses ranging from 1.8mg/kg to 2.8mg/kg. PSMA ADC was generally well tolerated in patients at doses up to and including 2.5mg/kg, the maximum tolerated dose. Dose limiting toxicities, primarily neutropenia, were seen at 2.8mg/kg. The most frequent adverse events were anorexia and fatigue. Progenics Pharmaceuticals initiated a phase II, open-label, multicenter study of PSMA ADC.
August 27, 2012
Medivation and Astellas Pharma published results from a phase III trial of enzalutamide for the treatment of metastatic castration-resistant prostate cancer. This international, randomized, double-blind, placebo-controlled study, AFFIRM, enrolled 1,199 men who had been previously treated with docetaxel-based chemotherapy. Subjects received enzalutamide 160mg once daily (as four 40mg capsules), or placebo. Data showed enzalutamide exhibited a statistically significant benefit in overall survival compared to placebo. Men treated with enzalutamide had a median overall survival of 18.4 months (95% confidence interval, 17.3 to not yet reached) compared to 13.6 months (95% confidence interval 11.3-15.8) for men treated with placebo (hazard ratio 0.63; p<0.0001), representing a 37% reduction in the risk of death. The drug was well tolerated. The most frequent adverse events were fatigue, diarrhea and hot flush. Seizure was reported in less than 1% of enzalutamide-treated patients. Neither Medivation nor Astellas noted its next steps for enzalutamide.
February 6, 2012
Medivation issued results from a phase III trial of MDV3100 for the treatment of prostate cancer. This placebo-controlled, double-blind, multinational trial, dubbed AFFIRM, enrolled 1,199 subjects with metastatic castration-resistant prostate cancer who had failed docetaxel-based chemotherapy. The subjects received MDV3100 160 mg orally once daily or placebo. The primary endpoint was overall survival. Data demonstrated a statistically significant improvement in overall survival compared to placebo (p<0.0001). The median survival for the MDV3100 arm was 18.4 months compared with 13.6 months for the placebo arm. MDV3100 also met all secondary endpoints, including radiographic progression-free survival (8.3 versus 2.9 months; p<0.0001), soft tissue response rate (28.9% versus 3.8%; p<0.0001) and time to prostate-specific antigen (PSA) progression (8.3 versus 3.0 months; p<0.0001).
October 3, 2011
Bayer Healthcare issued results from a phase III trial of radium-223 chloride for castration-resistant prostate cancer and symptomatic bone metastases. This double-blind, randomized, controlled study, dubbed ALSYMPCA (ALpharadin in SYMptomatic Prostate Cancer), enrolled 922 subjects with advanced, hormone-refractory prostate cancer that had metastasized to the skeleton. The subjects received Alpharadin plus best standard of care or placebo plus best standard of care. The primary endpoint was overall survival. The overall survival result was statistically significant, with a median overall survival of 14 months for radium-223 chloride and 11.2 months for placebo (p≡0.0022). The time to first skeletal related events was 13.6 months versus 8.4 months, a 64% improvement (p≡0.00046). Total alkaline phosphatase normalization was reached by 33% versus 1% of subjects (p<0.001) and radium-223 chloride resulted in a 49% improvement in time to prostate-specific antigen progression (p≡0.00015).
June 13, 2011
Algeta and Bayer reported interim results from a phase III trial of radium-223 chloride for the treatment of prostate cancer that has metastasized to the bone. This randomized, double-blind, multi-dose, placebo-controlled trial, ALSYMPCA, enrolled 922 subjects with symptomatic castration-resistant/hormone-refractory prostate cancer that had spread to the bone. The subjects received radium-223 or placebo plus current standard of care. The primary endpoint was overall survival. The overall survival result was statistically significant, with a median overall survival of 14 months for radium-223 chloride and 11.2 months for placebo (two-sided p-value≡0.0022).
February 28, 2011
Bellicum Pharmaceuticals issued results from a phase I/II trial of BP-101, a drug-activated dendritic cell vaccine for prostate cancer. This dose escalation study enrolled 12 subjects with metastatic castrate resistant prostate cancer. The subjects received BPX-101 in combination with activating agent AP1903, administered every other week for six doses. Responses were assessed at week 13. Treatment with BPX-101 and AP1903 resulted in RECIST Partial and Complete Responses in three of twelve (25%) subjects, including Complete Responses in subjects with visceral metastatic disease. Two of twelve (17%) subjects experienced PSA declines approaching 50% within the first 12 weeks of therapy. Both subjects experienced clinical, symptomatic improvement in conjunction with these PSA declines. Treatment with BPX-101 and AP1903 also elicited immunological responses in the majority of subjects evaluated. The combination of BPX-101 and AP1903 was safe and well tolerated at doses up to 25 million cells and 0.4 mg/kg respectively, at this dosing schedule.
October 18, 2010
Centocor Ortho Biotech released positive interim results from a phase III trial of abiraterone acetate for the treatment of castration-resistant prostate cancer. This randomized, double-blind placebo-controlled study, COU-AA-301, enrolled 1,195 subjects who received abiraterone acetate (1000 mg once daily) plus prednisone/prednisolone (5 mg twice daily) or placebo plus prednisone/prednisolone. The primary endpoint was overall survival. Treatment with abiraterone acetate resulted in a 35% reduction in the risk of death (p<0.0001) and a 36% increase in median survival (14.8 months vs. 10.9 months) compared with placebo. The subjects who received abiraterone acetate also showed significant improvements in secondary study endpoints compared to placebo, including time to prostate specific antigen (PSA) progression (10.2 months vs. 6.6 months) and increase in radiographic progression-free survival (median 5.6 months vs. 3.6 months). Total PSA response was achieved in 38% of subjects treated with abiraterone acetate versus 10% in the prednisone/prednisolone plus placebo group.
September 20, 2010
GtX released positive results from a phase II trial of GTx-758 for the treatment of prostate cancer. This open label trial enrolled 60 healthy male subjects who were randomized to receive one of three oral daily doses of GTx-758 (600 mg, 1000 mg or 1500 mg) until achieving medical castration or 56 days, whichever came first. Medical castration (levels of serum total testosterone <50 ng/dL) was achieved within three weeks in subjects both the 1000 mg and 1500 mg treatment arms. GTx-758 also increased serum SHBG (sex hormone binding globulin), and markedly reduced serum free testosterone. GTx-758 was well tolerated and no serious adverse events were reported.
March 8, 2010
Dendreon released positive long-term results from a phase III trial of Provenge, an immunotherapy for the treatment of prostate cancer. This multi-center, randomized, double-blind, placebo-controlled study, dubbed IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment), enrolled 512 subjects with asymptomatic or minimally symptomatic, metastatic, castrate-resistant prostate cancer. According to long term follow-up data (36.5 months and 349 deaths), Provenge increased three-year survival by 40% compared to placebo (32.1% versus 23%). The median survival difference of Provenge compared to placebo was maintained at 4.1 months, with a 24.1% reduction in the risk of death (p≡0.017).
Sanofi-aventis issued positive results from a phase III trial of cabazitaxel for the treatment of prostate cancer. This global trial, TROPIC, enrolled 755 subjects with metastatic hormone-refractory prostate cancer whose disease had progressed despite previous docetaxel-based chemotherapy. The subjects were randomized to receive cabazitaxel plus prednisone/prednisolone or mitoxantrone plus prednisone/prednisolone for up to a maximum of 10 cycles. The primary endpoint was overall survival. Results showed that the combination of cabazitaxel and prednisone/prednisolone significantly reduced the risk of death by 30% (p<0.0001) with a clinically meaningful improvement in the median overall survival of 15.1 months in the cabazitaxel combination arm versus 12.7 months in the mitoxantrone combination arm. The secondary endpoint of progression-free survival was also reached. The combination treatment with cabazitaxel resulted in a significant increase in median progression-free survival compared to mitoxantrone (2.8 months versus 1.4 months; p<0.0001).
February 15, 2010
Amgen reported positive results from a phase III study of denosumab for bone metastases resulting from prostate cancer. This international, head-to-head, randomized, double-blind study enrolled 1,901 men with bone metastases from hormone-refractory prostate cancer. The subjects received either 120 mg of denosumab subcutaneously every four weeks or 4 mg Zometa (standard of care) intravenously as a 15 minute infusion every four weeks. The primary endpoint was to determine if denosumab is non-inferior to Zometa with respect to the first on-study skeletal-related event (SRE's). The composite endpoint of four SREs- fracture, radiation to bone, surgery to bone, and spinal cord compression- was used to measure the effectiveness of denosumab versus Zometa. Denosumab demonstrated superiority over Zometa for both delaying the time to the first on-study SRE and reducing the rate of multiple SREs. Overall rates of adverse events and serious adverse events, including infections, were generally similar between the two arms.
April 27, 2009
Dendreon issued positive interim results from a phase III trial of Provenge for the treatment of prostate cancer. This US-based, randomized, double-blind, placebo-controlled trial, dubbed PROTECT (PROvenge Treatment and Early Cancer Treatment), enrolled 176 subjects with non-metastatic androgen-dependent prostate cancer who had a prostate-specific antigen (PSA) recurrence following surgical removal of the prostate. Following three months of hormone therapy, the subjects received Provenge of placebo at weeks zero, two and four. A treatment booster infusion of Provenge or placebo was offered after confirmed PSA greater than or equal to 3.0ng/mL. Immune responses were measured pre-treatment, at weeks four and 13, and at four and 13 weeks following the booster infusion. At the week zero dose of Provenge, the expression of CD54 on Antigen Presenting Cells (APCs) was upregulated 5.8 fold. At the week two dose, it was 10.1 fold, significantly increased from week 0 (p< 0.001). The increase in CD54 up-regulation continued at week four (10.7 fold) and at the time of the booster infusion (12.0 fold). There was an increase in cellular immune response between pre-treatment and week four (p< 0.001), which persisted through 13 weeks after the booster infusion (p<0.001). The Provenge booster infusions occurred at a median of 1.1 years after the week four dose.
March 9, 2009
Medivation issued positive results from an ongoing phase I/II trial of MDV3100 for the treatment of castration-resistant prostate cancer. To date, this US-based, open-label, dose-escalation trial had enrolled 140 subjects, both treatment nave and treatment experienced. The subjects had received MDV3100 up to 600 mg/day orally, once daily. Efficacy endpoints included circulating tumor cell (CTC) counts, serum prostate specific antigen (PSA) levels, soft tissue and bony metastases, and time on treatment. Data are from 114 subjects who had been followed for 12 weeks or longer. A majority of the subjects with favorable CTC counts (four or less) at the start of treatment maintained favorable counts at week 12 (89% and 100% of the chemotherapy naive and post-chemotherapy groups, respectively). A significant number of subjects with unfavorable CTC counts of five or higher at baseline converted to favorable counts of less than five at week 12 (73% and 40% of chemotherapy naive and post-chemotherapy groups, respectively). MDV3100 also produced significant PSA declines (50% or more from baseline) and radiographic control (partial response or stable disease) in both chemotherapy naive and post-chemotherapy subjects at week 12. In the chemotherapy nave population, 57% of the subjects exhibited a PSA decline, and 80% and 61% showed radiographic control of soft tissue and bony metastases, respectively. In the post-chemotherapy population, 45% of the subjects exhibited a PSA decline, and 70% and 64% showed radiographic control of soft tissue and bony metastases, respectively. To date, the median time on treatment for the chemotherapy-naive and post-chemotherapy populations is 276 and 145 days, respectively. Safety data from all 140 enrolled subjects showed MDV3100 has been generally well tolerated at doses of up to and including 240 mg/day. Based on the results, Medivation plans to move forward with phase III trials later in 2009.
June 9, 2008
OncoGenex reported positive preliminary results from a phase II trial of OGX-011 for the treatment of hormone refractory prostate cancer. This open-label, randomized, multicenter study evaluated 42 subjects who received mitoxantrone plus OGX-011 or docetaxel plus OGX-011. Subjects received a median of six cycles of mitoxantrone plus OGX-011 or eight cycles of docetaxel plus OGX-011. At median follow-up of 17.2 months following the start of second-line chemotherapy, approximately 38% of subjects were alive, with a median survival of 12.1 months. Median survival was estimated at 11.4 months in the mitoxantrone plus OGX-011 group and 14.7 months in the docetaxel plus OGX-011 group. Post-treatment serum clusterin levels showed significant reduction compared to baseline levels (p < 0.0001) and the average serum clusterin levels were predictive of survival, with low-average levels predicting median survival time of 14.7 months compared to high-average levels predicting median survival time of 5.5 months. Reductions in pain or analgesic use were seen in 46% of evaluable patients treated with mitoxantrone plus OGX-011 with a median duration of 5.8 months and in 61% of evaluable patients retreated with docetaxel plus OGX-011 with a median duration of 6.2 months. Both treatment groups achieved prostate specific antigen (PSA) declines of at least 50%: 27% of subjects treated with mitoxantrone plus OGX-011 and 40% of subjects treated with docetaxel plus OGX-011.
April 28, 2008
Spectrum reported positive results from a phase IIb trial of ozarelix for the treatment of prostate cancer. This nine-month, randomized, double-blind, placebo-controlled study enrolled seventy six subjects in North America. The subjects received either ozarelix 15mg or placebo on day zero and fourteen following a two injection, four week placebo run-in period. The primary endpoint was the improvement in lower urinary tract symptoms secondary to BPH as measured by the International Prostate Symptom Score (IPSS). Secondary endpoints included measurements in Peak Urine Flow (Qmax), Erectile Function and Quality of Life. In the ITT population, the improvement in IPSS at twelve weeks was 4.4 in placebo group and 2.9 in the ozarelix group, and did not reach statistical significance (p=0.37). Ozarelix demonstrated a numerical improvement in Peak Urine Flow (2.5mL/sec) compared to placebo (1.3mL/sec) at twelve weeks, but did not reach statistical significance (p=0.41). In the per-protocol analysis, ozarelix demonstrated a clinically meaningful improvement in IPSS of 6.0 compared to 3.0 for placebo. This improvement was observed as early as eight weeks, approached statistical significance (p=0.09) and the effect was observed out to thirty six weeks. Ozarelix demonstrated a numerical improvement in peak urine flow (1.6mL/sec) as early as four weeks, compared to no change in placebo (0.0mL/sec), (p=0.14), however this difference was not consistently seen at later time points. Based on the results Spectrum plans to conduct another phase IIb trial shortly.
April 21, 2008
Cell Genesys reported positive results from a phase I/II trial of GVAX for the treatment of prostate cancer. This open-label trial enrolled nineteen men with non-castrate (hormone-sensitive) prostate cancer with PSA recurrence following prostatectomy and/or radiation therapy, and no radiologic evidence of metastases. The subjects received an initial dose of GVAX followed by bi-weekly injections for a six-month period. They were monitored for an additional six months following the last injection for adverse events, PSA response, changes in PSA kinetics, and the induction of prostate cancer-associated antibodies. GVAX resulted in a statistically significant increase in median PSA doubling time as well as the formation of prostate cancer-associated antibodies in 79% of subjects who received the treatment. There was an increase in PSA doubling time from 28.7 weeks before receiving GVAX immunotherapy to 57.1 weeks after receiving therapy (p=0.0095). In addition, sixteen subjects (84%) experienced a decline in PSA slope, a potential measure of the rate of disease progression, after receiving GVAX (p=0.018). PSA levels in eight of nineteen subjects (42%) remained stable during the six-month treatment period, with a median time to PSA progression of 9.7 months. In addition, analysis of patient sera taken before and after receiving GVAX showed that fifteen of the nineteen subjects (79%) developed new or enhanced antibody responses against either PC-3 or LNCaP, the two prostate cancer cell lines that comprise GVAX. Treatment was generally well tolerated, with the most common side effects being injection site reactions.
March 31, 2008
Oxford BioMedica issued positive results from a phase II trial of TroVax for the treatment of prostate cancer. This trial enrolled twenty seven subjects with metastatic hormone-refractory prostate cancer (HRPC). The subjects were treated with TroVax as a single agent, administered in ten intramuscular injections over forty-five weeks, or in combination with standard therapy of granulocyte macrophage-colony stimulating factor (GM-CSF). All twenty-four evaluable subjects mounted robust antibody responses against the targeted tumor antigen, 5T4, and nine subjects also showed strong 5T4-specific T-cell responses. Twenty subjects (83%) experienced disease stabilization. At this time disease stabilization ranged from two to more than ten months. Time to disease progression (TTP) was significantly greater in 5T4-specific T-cell responders compared to non-responders, with a median TTP of 5.6 months versus 2.3 months (p = 0.028). The combination of GM-CSF with TroVax showed similar clinical and immunological responses to TroVax alone. Based on the results, Oxford Biomedica initiated a second phase II study evaluating TroVax as a first line therapy.
March 3, 2008
GTx issued positive results from a phase III trial of toremifene citrate for the treatment of multiple side effects of androgen deprivation therapy (ADT) for advanced prostate cancer. This two year double-blind, placebo-controlled study randomized study enrolled one thousand three hundred and eighty nine subjects undergoing ADT in the United States and Mexico. The subjects received toremifene at 80 mg or placebo. The primary endpoint was new morphometric vertebral fractures read by an independent third party. Other key endpoints included bone mineral density, lipid changes, hot flashes, and gynecomastia. In the modified intent-to-treat group (all subjects with at least one evaluable study radiograph and a minimum of one dose of study drug or placebo), toremifene demonstrated a 50% reduction in morphometric vertebral fractures (p less than 0.05; 5% fracture rate in the placebo group). The estimated two year fracture rate for new morphometric vertebral fractures in the placebo group was 6.2%. In an intent to treat analysis which included all subjects randomized into the trial, toremifene citrate demonstrated a 53% reduction in new morphometric vertebral fractures (p=0.034; 3.6% fracture rate in the placebo group). Toremifene citrate demonstrated statistically significant increases in bone mineral density in the lumbar spine, hip, and femur skeletal sites when compared to placebo (p less than 0.0001 for each). In addition, when compared to placebo toremifene citrate also resulted in a decrease in total cholesterol (p=0.011), LDL (p=0.018), and triglycerides (p less than 0.0001), and an increase in HDL (p=0.001). There were also statistically significant improvements in gynecomastia (p=0.003). Based on the results, GTx plans to file an NDA with the FDA by the summer of 2008.
February 25, 2008
Cell Genesys reported positive results from a phase II trial of GVAX for the treatment of prostate cancer. The analysis was designed to evaluate the potential association between immune responses to GVAX and increased survival. The study enrolled eighty subjects, sixty five of whom had their serum evaluated to determine each subjects' immune response to two specific antigens, HLA-A24 and FLJ14668, following GVAX treatment. Of the sixty five subjects, thirty four demonstrated an FLJ14668-specific antibody immune response and had a median survival of forty three months. The median survival of subjects who did not generate the anti-FLJ14668 antibodies was twenty one months (p=0.002). Twenty-two of these sixty five subjects received a dose of GVAX comparable to that being evaluated in ongoing phase III prostate cancer trials. Of these twenty two subjects, sixteen (73%) mounted an immune response to FLJ14668. These sixteen subjects achieved a median survival of 44.9 months. The median survival for all twenty two subjects in this treatment group was thirty five months. Of the fifty eight subjects who were HLA-A24 genotype negative and therefore potentially able to mount anti-HLA-A24 specific antibody responses, thirty subjects were found to be anti-HLA-A24 antibody positive. These thirty had a median survival of forty three months, compared to a median survival of eighteen months in the subjects who did not generate anti-HLA-A24 antibodies (p=0.05). Phase III trials are currently underway.
Northwest Bio announced long-term follow-up data from phase I and phase I/II trials of DCVax-Brain for the treatment of Glioblastoma multiforme (GBM). Data is from 19 subjects with newly diagnosed Glioblastoma multiforme who received surgery followed by DCVax-Brain plus standard of care (a combination of radiation and daily Temodar chemotherapy and then 6 monthly cycles of Temodar chemotherapy). Eight of 19 subjects were still alive (ranging from 24.5 months to 92 months), with median overall survival in all subjects of 33.8 months compared to 17 months in subjects who received standard of care alone (p < 0.0079). Five of the 8 subjects who were still alive showed no signs of cancer recurrence, with follow-up time ranging from 41 months to 92 months. The median time to progression was 18.1 months, compared to 8.1 months for subjects receiving standard of care alone (p = 0.00001). To date, 68% of subjects receiving DCVax-Brain in addition to Standard of Care have lived longer than 2 years, 42% have lived longer than 3 years, and 26% have lived longer than 4 years (48, 54, 57, 62 and 92 months so far). Phase II trials of DCVax-Brain are currently underway.
OncoGenex issued positive interim results from a phase II trial of OGX-011 for the treatment of prostate cancer. This open-label, randomized, multicenter study evaluated 43 subjects who received OGX-011 in combination with docetaxel or mitoxantrone, administered as second-line chemotherapy. The subjects underwent a median of 6 cycles of mitoxantrone or 7.5 cycles of docetaxel. To date, with a median follow-up of 13.3 months, in both arms of the trial approximately 30% of subjects have not manifested disease progression and approximately 60% of subjects are alive. Median survival has not been reached in either arm. Reductions in pain or analgesic use were seen in 50% of evaluable subjects treated with mitoxantrone and in 67% of evaluable subjects treated with docetaxel. Based on the results, a phase III trial design is underway.
November 5, 2007
Cougar Biotechnology issued positive results from a phase I trial of CB7630 for the treatment of prostate cancer. This dose-ranging trial enrolled twenty-seven subjects with chemotherapy-nave, castration refractory prostate cancer (CRPC). Eighteen subjects received once daily doses of CB7630 on an empty stomach and nine received CB7630 on a full stomach (with a high fat calorie meal). Overall, of the twenty-seven subjects, sixteen (59%) experienced a greater than 50% decline in prostate specific antigen (PSA) levels. Furthermore, eleven of the eighteen subjects (61%) in the fasted group and five of the nine subjects (56%) in the fed group experienced a greater than 50% decline in PSA levels. Treatment with CB7630 was found to be well tolerated in both groups and the safety profile was unaffected by administration of the drug with food. Based on the results, Cougar plans to continue with the development of CB7630.Cougar Biotechnology issued positive results from a phase I trial of CB7630 for the treatment of prostate cancer. This dose-ranging trial enrolled twenty-seven subjects with chemotherapy-nave, castration refractory prostate cancer (CRPC). Eighteen subjects received once daily doses of CB7630 on an empty stomach and nine received CB7630 on a full stomach (with a high fat calorie meal). Overall, of the twenty-seven subjects, sixteen (59%) experienced a greater than 50% decline in prostate specific antigen (PSA) levels. Furthermore, eleven of the eighteen subjects (61%) in the fasted group and five of the nine subjects (56%) in the fed group experienced a greater than 50% decline in PSA levels. Treatment with CB7630 was found to be well tolerated in both groups and the safety profile was unaffected by administration of the drug with food. Based on the results, Cougar plans to continue with the development of CB7630.
GenVec reported positive interim results from a phase II trial of TNFerade for the treatment of colorectal cancer. This trial enrolled seven subjects who received TNFerade administered weekly via intratumoral injections during the first five weeks of radiotherapy. All subjects also received oral capecitabine twice daily during radiotherapy. Surgical removal if the tumor was performed six to nine weeks following therapy. Prior to treatment, four of the seven subjects were classified as highly likely to need sphincter removing surgery with colostomy. Following treatment with TNFerade, all seven subjects who underwent surgical resection had successful sphincter sparing procedures. In addition, five of the seven subjects showed complete response. Based on the data, GenVec plans to continue the development of TNFerade for this indication.
Infinity and MedImmune released positive preliminary results from a phase I/II trial of IPI-504 for the treatment of non-small cell lung cancer. In the phase I portion of this open label trial, 12 subjects who received IPI-504 at three dose levels (150, 225, and 300 mg/m2) on a four-week cycle, consisting of twice-weekly dose administration with no break in treatment. Of the 12 subjects, 9 were evaluable for response. Stable disease, as measured via RECIST (Response Evaluation Criteria in Solid Tumors), was achieved over at least one cycle of administration in 7 subjects, one of whom experienced extended stable disease over seven cycles (twenty-seven weeks). In addition, four subjects underwent PET imaging. All four showed a decrease in tumor metabolic activity in response to IPI-504 administration, as measured by uptake of 18-fluorodeoxyglucose. Treatment was well tolerated at doses up to 225 mg/m2. The phase II portion is expected to begin by the end of 2007.
Pharmion and GPC Biotech issued negative results form a phase III trial of satraplatin for the treatment of prostate cancer. This double-blinded, randomized, placebo controlled trial enrolled 950 subjects with hormone-refractory prostate cancer. The trial was designed to compare satraplatin plus prednisone or placebo plus prednisone as a second-line treatment for prostate cancer. The primary endpoint of overall survival was not achieved (p=0.80, stratified log rank analysis). The median overall survival was 61.3 weeks for the satraplatin arm compared to 61.4 weeks for the control group and the hazard ratio was 0.97 (95% CI: 0.83, 1.13). The companies plan to fully evaluate the data in order to determine future development plans.
September 17, 2007
Ardana announced positive preliminary results from a phase II trial of teverelix for the treatment of prostate cancer. This 8-week randomized trial enrolled 38 subjects who received either low dose or high dose teverelix. The primary endpoint was duration of testosterone suppression to below castration level (< 0.5 ng/ml). Secondary endpoints included the percentage of subjects attaining and maintaining medical castration, an evaluation of prostate specific antigen (PSA) and luteinizing hormone levels, and local and systemic tolerability of the drug. By day three, testosterone suppression was attained in 14 and 18 subjects in the low- and high-dose groups, respectively. A total of 19 high-dose-treated subjects had a reduction of testosterone levels to castration level, the duration of which was between 54 to 147 days, with 17 subjects being castrated for 8 weeks or more. In addition, at week 4 normalized PSA (< 4.0 ng/ml) levels were observed in 74% of the high dose group and mean PSA levels were normalized at 8 weeks. Based on the results, Ardana plans to advance the development of teverelix.
AstraZeneca released positive results from a phase III trial of Iressa for the treatment of non-small cell lung cancer (nsclc). This trial was dubbed INTEREST (IRESSA Non-small-cell lung cancer Trial Evaluating REsponse and Survival against Taxotere) and enrolled 1,446 subjects with pre-treated nsclc. The trial was designed to compare the overall survival of subjects treated with oral Iressa to intravenous docetaxel. The results established non-inferiority between Iressa and docetaxel. In addition, Iressa demonstrated a more favorable tolerability profile and superior quality of life for subjects versus docetaxel. Iressa has been approved for the treatment of nsclc in several international markets.
EntreMed issued positive interim results from a phase II trial of MKC-1 for the treatment of metastatic breast cancer. This single agent trial enrolled 40 subjects with metastatic breast cancer who had failed therapy with anthracyclines and taxanes. The subjects received orally administered MKC-1 (125 mg/m2) twice-daily on a 28 day dosing schedule. Of 35 evaluable subjects there was one complete response, two partial responses and three stable diseases of greater than four months. Based on the results the second stage of this trial has commenced and is enrolling an additional 53 subjects to assess objective response rates.
September 3, 2007
Ascenta issued positive interim results from a phase I/II trial of AT-101 for the treatment of prostate cancer. This open-label trial enrolled men with hormone-refractory-prostate cancer who received AT-101 in combination with docetaxel and prednisone. Results from the phase I portion showed eight of nine chemotherapy-naive subjects (89%) treated achieved a 50% partial response and all nine achieved a 30% drop in PSA levels. No dose-limiting toxicities were observed. The phase II portion of the trial is currently underway.
August 6, 2007
Genzyme reported positive results from a phase III trial of Mozobil for the treatment of multiple myeloma. This randomized, double-blind, placebo-controlled trial enrolled 302 subjects who were undergoing a hematopoietic stem cell transplant (HSCT) for multiple myeloma. Subjects were treated with Mozobil following granulocyte-colony stimulating factor (G- CSF) or placebo following G-CSF. In the primary efficacy endpoint, 72% of subjects treated with Mozobil and G-CSF achieved the target threshold for collection of at least 6 million CD34+cells/kg from the peripheral blood with two days or fewer of apheresis sessions, compared with 34% of subjects in the G-CSF/placebo group (p<0.0001). Secondary endpoint were achieved as well; the median number of days to achieve the target of 6 million cells was one day for the Mozobil/G-CSF group and four days for the G-CSF/placebo group. Genzyme plans to file for US and European regulatory approval in the first half of 2008.
Oncogenics and Isis released positive preliminary results from a phase II trial of OGX-011 for the treatment of metastatic hormone refractory prostate cancer. This trial enrolled 42 subjects who were randomized to receive 640 mg/week OGX-011 plus prednisone plus either mitoxantrone or docetaxel. The results are from a median follow-up of 7.4 months. In the cohort receiving OGX-011 plus docetaxel: death occurred in 10% of the population, 30% experienced disease progression, 35% had a 50 percent decrease in prostate specific antigen (PSA), and 55% had a 30 percent decrease in PSA. In the cohort receiving OGX-011 plus mitoxantrone: death occurred in 32% of the population, 59% experienced disease progression, 23% had a 50 percent decrease in PSA and 32% had a 30 percent decrease in PSA. Treatment in both arms was generally well tolerated. Based on the results, Oncogenics is planning phase III trials of OGX- 011 in combination with docetaxel.
Pharmion announced positive results from a phase III trial of Vidaza for the treatment of myelodysplastic syndromes. This trial was designed to compare Vidaza to conventional care regimens (CCR), including best supportive care (BSC) alone, low-dose cytarabine plus BSC or standard chemotherapy plus BSC) utilized in the control arm. In the primary endpoint analysis, Vidaza was associated with a median survival of 24.4 months versus 15 months for those receiving CCR treatment, an improvement of 9.4 months with a stratified log-rank p-value of 0.0001. Two-year survival rates were 50.8% versus 26.2% for subjects receiving Vidaza versus CCR (p<0.0001). Based on the results, Pharmion plans to file a MAA in Europe and a sNDA in the US by the end of 2007.
March 5, 2007
Antisoma announced positive interim results from a phase II trial of ASI404 for the treatment of prostate cancer. This trial enrolled 74 male subjects who were randomized to receive AS1404 plus docetaxel or docetaxel alone (1200 mg/m2). The subjects receiving the combination therapy had a higher PSA response at 57% versus 35% for those on docetaxel alone. The addition of AS1404 to chemotherapy also produced a near halving in the frequency of progression judged by PSA when compared to docetaxel alone (17% versus 29%, respectively). Full results from this trial are expected by the end of 2007.
Cell Geneseys and Medarex reported positive interim results from a phase I study of GVAX in combination with Medarex's investigational monoclonal antibody MDX-010, for the treatment of prostate cancer. The data from this dose escalation trial was collected from 12 subjects who have completed treatment to date. The primary endpoints of the study included safety and the determination of a maximum tolerated dose for the combination therapy. Efficacy endpoints were time to clinical disease progression, time to prostate-specific antigen (PSA) progression and PSA response, immune response to GVAX, reduction in metabolic bone activity and survival. Of the six subjects treated in the two highest dose groups, antitumor activity was observed in five, including PSA declines of greater than 50% that were maintained in four of these subjects for at least six months. The longest response is ongoing at more than 12 months. Two additional subjects have had ongoing stable disease on bone scan for at least three months. In addition, the combination therapy enhanced T cell and dendritic cell activity, which was more pronounced at the higher dose levels. The maximum tolerated dose has not been reached at this time. The companies plan to use this data to support the continuing development of this combination therapy in current phase III trials.
Threshold issued negative results from a phase III trial of glufosfamide for the treatment of pancreatic cancer. This randomized, open-label trial enrolled 303 subjects with metastatic pancreatic cancer who had relapsed after standard gemicitabine-containing systemic chemotherapy. Subjects received glufosfamide every three weeks plus best supportive care (BSC) or best supportive care alone. The primary endpoint, statistically significant difference in overall survival compared to BSC, was not met, with a median survival of 105 days for the glufosfamide arm and 84 days for the BSC arm (p=0.19). Based on the results Threshold plans to discontinue the development of glufosfamide for this indication.
January 22, 2007
Point Therapeutics issued positive preliminary results from a phase II trial of talabostat plus gemcitabine for the treatment of pancreatic cancer. This single-arm trial enrolled 60 subjects with metastatic pancreatic cancer who had not received prior chemotherapy. Treatment was well tolerated with no unexpected adverse events. The primary endpoint was six-month survival. Secondary endpoints included overall survival, progression-free survival and quality of life. Of the 21 evaluable subjects 48% survived more than six months. Of the 31 subjects evaluable for tumor response, three demonstrated a clinical response to treatment, including one complete response and two partial responses. Based on the results, Point will advance this trial to completion.
Protox released positive interim results from a phase I trial of PRX302 for the treatment of prostate cancer. Data was reported from 12 subjects treated to date who received PRX302 injected directly into the prostate. Treatment was well tolerated with no evidence of toxicity or adverse events. Efficacy was determined by measuring PSA (prostate specific antigen) levels throughout the study and conducting prostate biopsies at 30 days post-treatment. Early analysis revealed that eight of the nine subjects for whom 90 day data was available reported a decrease in PSA levels compared to baseline during at least one of the 14-, 30-, 60- or 90-day follow-up intervals. For six of the nine subjects, PSA levels continued to fall through day 90 by 6% to 42% compared to baseline. Biopsies taken at 30 days post-treatment showed an average decrease in cancer positive biopsies of 36% when compared to baseline, with four subjects showing a 50% reduction and two subjects with a 100% reduction. Protox expected to complete this trial by mid-2007 and initiate a phase II trial by the end of 2007.
October 16, 2006
Cougar issued positive results from a phase I trial of CB7630 for the treatment of castration refractory prostate cancer (CRPC). This trial enrolled 14 hormone refractory, chemotherapy-naïve subjects who received CB7630 in escalating doses, once a day. Treatment was well tolerated, with minimal toxicity at doses as high as 2000 mg/day. Antitumor activity was evaluable in 12 subjects and of these, 8 (67%) experienced a confirmed decline in prostate specific antigen (PSA) levels of greater than 50% and 6 (50%) experienced PSA declines of greater than 90%. Measurable tumor lesions were evaluable in 5 subjects and of these, 3 (60%) showed partial radiological responses after treatment with CB7630. Based on this data, Cougar plans to move this drug into further development.
October 2, 2006
GPC and Pharmion announced positive results from a phase III trial, dubbed SPARC, of satraplatin as a second line treatment for hormone-refractory prostate cancer (HRPC). This double-blinded, randomized, placebo-controlled trial enrolled 950 subjects across 200 international sites. Subjects received satraplatin plus prednisone or placebo plus prednisone. Treatment was well tolerated with reported adverse events mild to moderate in severity. Efficacy data revealed that subjects who received satraplatin plus prednisone had a 40% reduction in the risk of disease progression compared with subjects who received prednisone plus placebo. Progression free survival in the subjects treated with satraplatin increased over time. Six month data demonstrated that 30% of the treated subjects showed no disease progression versus 17% of the subjects in the control arm. At 12 months 16% of the treated subjects had not progressed versus 7% of those in the control arm. A competed rolling NDA submission was expected by the end of 2006.
August 7, 2006
AEterna Zentaris and Spectrum Pharmaceuticals reported positive results of a phase II trial of ozarelix (D-63153), their luteinizing hormone releasing hormone (LHRH) antagonist for the treatment of hormone dependent prostate cancer. Trial data met their primary efficacy endpoint, establishing that cycles of 130 mg of the drug suppressed testosterone to castration-equivalent levels (< 0.5 ng/ml) for three months. In patients with castration-level suppression, serum PSA was reduced by at least 50% in 97% of subjects, compared to baseline. This open-label, randomized-controlled study enrolled 64 patients, who received one of three doses of the drug (65 mg, 100 mg 0r 130 mg) via intramuscular injection on varying 28-day dosing schedules for 3 treatment cycles. Additional results from the study were to be presented at the upcoming SIU (Societe Internationale D'Urologie) meeting in Cape Town, South Africa, on November 12, 2006.
Aida Pharmaceuticals has issued positive results of a phase I trial of Rh-Apo2L, their investigational gene therapy product for the treatment of malignant tumors. Preliminary efficacy data indicated that the drug reduced tumor size in non-Hodgkin lymphoma, sarcoma and adrenal gland cortical tumors, and affected tumor size in non-small cell lung cancer, colorectal cancer and parotid gland capsule adenocarcinoma. Treatment was generally well tolerated with no evidence of hematological toxicity observed. The study enrolled 20 patients at the Chinese Academy of Medical Sciences Oncology Hospital in Beijing, China. Based on these results, the company announced plans to apply for clearance from the SFDA to initiate phase II and III trials in the near future, with projected completion of all studies before the end of 2007.
January 23, 2006
Breakthrough Therapeutics issued positive interim results of a clinical trial of CMLVAX100, for the treatment of chronic myeloid leukemia (CML). Results of the study indicated that the vaccine was immunogenic in 94% (n=17/18) subjects, producing peptide specific T-cell response. 6 of 10 patients who presented cytogenetic evidence of CML on enrollment experienced complete cytogenic response, and 3 achieved undetectable levels of disease biomarker (bcr-abl transcript). Adverse events were limited to injection-site reactions. This open-label study enrolled 21 patients with stable residual disease following treatment with imatinib, who received 6 vaccinations 2 weeks apart, with additional doses every 4-6 months for positive responders.
GTx has reported positive interim results of a pair of phase III trials of Acapodene (toremifene citrate), for the prevention of prostate cancer, and for the treatment of adverse events associated with androgen deprivation therapy (ADT) for prostate cancer. Preliminary safety data from the fist study were sufficiently positive for the trial's drug safety monitoring board (DSMB) to recommend that the study continue unchanged. Initial results from the second study yielded significant improvements in bone mineral density in the lumbar spine (+2.3%; p<0.001), the hip (+2.0%; p=0.001), and the femur (+1.5%; p=0.009) , vs. placebo. Continuation of the second study was also recommended by its DSMB. The first study enrolled 1,260 men with prostatic intraepithelial neoplasia across 130 sites in the US, Canada, Mexico and Argentina; subjects received 20 mg of the drug or placebo daily. The second study enrolled 1,388 patients on ADT across 150 sites in the US and Mexico, who received 80 mg oral Acapodene or placebo daily.
October 31, 2005
Procyon BioPharma has issued positive interim results of a dose-finding study of PCK3145, for the treatment of prostate cancer. Trial results have demonstrated a positive overall tolerability profile, with no serious adverse events reported to date. Preliminary bioactivity data yielded reductions in plasma levels of the metastatic enzyme matrix metalloproteinase-9 (MMP-9). Efficacy results from one patient demonstrated stable levels of prostate-specific antigen and tumor growth scans through 4 treatment cycles. This ongoing, open-label study planned to enroll a total of 20 subjects, who were randomized 1:1 to receive either 7.5mg/m2 twice weekly or 15mg/m2 once weekly for 4 weeks, followed by 2 weeks off treatment. The company announced that 4 subjects remained to be enrolled, and successful completion of this trial was to inform the optimum dose regimen for upcoming North American phase II trials.
Roche has reported positive results of a phase III trial of MabThera (rituximab) for the treatment of relapsed indolent non-Hodgkin's lymphoma (NHL). The drug is currently approved in both the US (as Rituxan) and EU for the acute treatment of NHL. Trial data indicated that continued administration of the drug as a single-agent maintenance treatment for NHL yielded significant improvements in 2-year progression free survival rates following initial treatment with MabThera and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. This open- label extension study enrolled 485 subjects from the initial acute-treatment study, who received MabThera via infusion once every 3 months or no additional treatment. Based on these results, this extension study was terminated to allow all subjects to receive the drug; final data were to be presented in December 2005 at the annual meeting of the American Society of Hematology.
October 3, 2005
EntreMed announced positive results of a phase II trial of Panzem (2-methoxyestradiol), for the treatment of hormone-refractory prostate cancer, in the journal Clinical Cancer Research. Study results indicated potential clinical utility, with 7 subjects in the high dose cohort and 1 in the low-dose cohort achieving 21-40% reductions in serum prostate-specific antigen levels (PSA). Both doses were well tolerated. This double-blind, randomized study enrolled 33 patients, who received one of 2 doses of the drug (400 mg or 1200 mg) daily via oral capsules until evidence of disease progression was found. The company announced that based on these results they planned to continue developing Panzem for this indication.
September 12, 2005
GlycoGenesys has reported positive interim results of a phase I trial of their investigational their galectin-3-targeted drug GCS-100, for the treatment of solid tumors. The trial met its primary objective of establishing the maximum tolerated dose for the treatment regimen. Preliminary safety data from the first 17 patients yielded a positive overall tolerability profile, with a dose limiting toxicity of a steroid-manageable rash. The drug also demonstrated a linear pharmacokinetic profile, and clinically relevant plasma concentrations were safely achieved. Preliminary efficacy data yielded stable disease in 11 of 14 evaluable subjects, lasting from 1.5 to more than 8 months; 3 of the stable patients were non- responsive to previous therapies. This ongoing open-label study had enrolled 22 patients to date at 2 sites in the US, who received escalating doses of the drug on a 5-days-on, 2-weeks-off treatment schedule. Based on these results, a phase I/II trial of the drug for the treatment of chronic lymphocytic leukemia is scheduled to begin by October 2005.
OncoGenex reported positive results of a phase I trial of OGX-011, for the treatment of prostate cancer, in the Journal of the National Cancer Institute. The trial met its primary pharmacokinetic endpoint, establishing the optimum dose for future phase II trials (640 mg). Success in secondary endpoints was also noted, including a significant and predictable increase in peak plasma concentration (p<0.001), significantly dose-related peak drug concentrations in prostate tissue (p<0.001), and a significant reduction expression of the drugs target protein clusterin, by more than 90% (p=0.008). Clusterin reduction at the optimum dose lead to a significant increase in apoptotic tumor cell death (21.2%, p<0.001). The study enrolled patients through the National Cancer Institute of Canada Clinical Trials Group, who received dose-ranging infusions of the drug prior to radical prostatectomy.
August 29, 2005
OXiGENE reported positive results from a phase Ib trial with Combretastatin A4 Prodrug (CA4P), a vascular disruption agent being investigated for the treatment of cancer. Results showed that 7 out of 12 subjects with ovarian cancer showed a tumor response, defined by RECIST or CA125 measurements. Partial responses have been seen in patients with small cell lung cancer and esophageal cancer, and disease stabilization was seen in a patient with rapidly progressing renal papillary cancer. The drug appears to be well tolerated and that no drug-related, serious adverse events occurred. The most common side effects observed are headache, fatigue and transient hyper- or hypotension, but no cardiac toxicity. The ongoing trial enrolled 41 subjects and is studying the administration of (CA4P) in combination with carboplatin or paclitaxel chemotherapy in patients with advanced cancer. Full results were presented at the 9th International Workshop on the Tumor Microenvironment Meeting being held at Christ Church College in Oxford, United Kingdom.
Salix Pharmaceuticals announced results from a trials investigating Colazal (balsalazide), an approved anti- inflammatory drug, for the potential treatment of radiation- induced proctosigmoiditis (RIPS) in patients undergoing radiation therapy for prostate cancer. According to results, the treatment showed dramatic reduction in radiation-induced proctosigmoiditis that we observed in patients receiving Colazol and the incidence and severity of proctitis was decreased by more than half in patients receiving balsalazide compared to patients to placebo. The double- blind, placebo-controlled, randomized trial enrolled patients with prostate cancer were given three balsalazide 750 mg capsules, or placebo, twice daily beginning 5 days prior to radiation therapy, throughout the course of radiation therapy, and continuing for 2 weeks after therapy. Results were published in the International Journal of Radiation Oncology-Biology-Physics.
June 27, 2005
Onyvax reported positive results from the second study cohort in a phase II trial of their investigational prostate cancer vaccine Onyvax-P. Results from the study yielded evidence of efficacy, with 42% of patients achieving statistically significant reduction in prostate specific antigen velocity, and an improvement in median time to disease progression to 58 weeks, vs. a historical baseline of 26-29 weeks. No significant toxicity was noted. This open-label study enrolled 13 patients with hormone-resistant prostate cancer (HRPC). Based on these results, the company announced plans to initiate phase IIb/III trials of the drug before the end of 2005.
pSivida has issued positive results of a phase IIa trial of BrachySil, their investigational brachytherapy for the treatment of liver cancer. Trial data met primary safety endpoints, with no serious adverse events noted and a positive overall tolerability profile. Secondary efficacy measures indicated that the drug was efficacious in inducing tumor regression in targeted lesions, including some 100% regressions. This open-label study enrolled 8 patients with inoperable liver tumors at the Singapore General Hospital, who received BrachySil implantations, with 3 and 6 month observational follow-ups. The company announced plans to initiate a multi-center, dose-escalating phase IIb trial of the drug in the second half of 2005.
May 23, 2005
Cell Therapeutics issued positive preliminary results of a phase II trial of Xyotax (paclitaxel poliglumex), for the first-line treatment of ovarian cancer. Results from the induction phase of the study indicated that the drug produced an 85% complete response rate, with an additional 12% of subjects experiencing partial response. This 98% response rate was superior to a historical baseline response rate of 80%. This open-label study enrolled 82 patients with treatment naíve stage III/IV ovarian cancer, who received Xyotax in combination with carboplatin on day 1 of a 21 day cycle for 6 cycles.
GTx reported positive results of a phase IIb trial of Acapodene (toremifene citrate), for the prevention of prostate cancer. The drug was previously approved as a treatment for advanced breast cancer. Trial data indicated efficacy in the trial's primary endpoint, producing a 48% reduction in prostate cancer incidence at 12 months in the lowest dosing group, vs. placebo (p=0.45). The higher two dosing groups both produced non- significant reductions in disease incidence. This 4- arm, double blind, placebo-controlled study enrolled 514 patients with high grade prostatic intraepithelial neoplasia (a prostate cancer risk factor) across 64 US sites, who received one of 3 oral doses of Acapodene (20 mg, 40 mg or 60 mg) or placebo once daily for one year.
Regeneron announced preliminary results of a phase I trial of VEGF Trap, for the treatment of advanced cancers. The drug's overall safety profile was positive, with most toxicity issues observed to be mild to moderate, though occasional incidence of serious adverse reactions, including hypertension, was observed. Maximum tolerated dose had not yet been reached. Preliminary evidence of biological activity and efficacy were observed, with VEGF Trap administration producing rapid tumor vascular response and some evidence of efficacy (1 partial response, 2 minor responses and 1 stable disease). This open-label single-agent study had enrolled 27 patients to date, who received one of five dose levels of the drug.
Schering and Novartis reported preliminary results of their phase III "CONFIRM-1" trial of PTZ/ZK (vatalinib), for the treatment of colorectal cancer. Trial data failed to meet their primary endpoint, with the drug producing a non-significant 12% decrease in risk of disease progression (p=0.118), as assessed by central data review. Secondary efficacy was noted, with investigator review producing a 17% reduction in risk of progression (p=0.026); higher efficacy was also noted among subjects with high levels of serum lactate dehydrogenase. Overall tolerability was generally positive, with adverse events generally similar to other VEGF inhibitors. This randomized, double-blind, placebo-controlled study enrolled 1168 subjects, who received an oral dose of either 1250 mg PTK/ZK or placebo once daily, in combination with standard FOLFOX4 chemotherapy. The companies announced that these data, in combination with upcoming data from their CONFIRM-2 phase III trial, would form the basis of regulatory submission in early 2007.
Transgene issued positive results of a phase II trial of their investigational vaccine candidate MVA-MUC1- IL2, for the treatment of non-small cell lung cancer (NSCLC). Trial data yielded preliminary evidence of efficacy, with 37% of subjects experiencing a partial response (PR), 71% of subjects achieving stable disease (PR or stable disease), median time to progression of 6.4 months, median survival of 13 months, and a 53% 1 year survival rate. Furthermore, subjects demonstrating immune response against the MUC1 tumor protein experienced significantly better overall survival (p=0.0035). This open-label study enrolled 44 patients with stage IIIB/IV NSCLC, who received MVA-MUC1-IL2 in combination with cisplatin and vinorelbine chemotherapy.
February 28, 2005
Australian Cancer Technology (AustCancer) has reported positive preliminary results from a phase I trial of their investigational immunostimulatory vaccine adjuvant GPI-0100, for the treatment of prostate cancer. Trial data indicated that all vaccine formulations of the drug were observed to be safe and well tolerated, with injection site reactions observed most often. Adverse events were observed more often among subjects receiving higher doses of more highly purified GPI-0100, but significantly less pain, inflammation and systemic symptoms were noted for all GPI-0100 groups vs. subjects receiving QS-21, an approved adjuvant. GPI-0100 produced non-inferior antibody titer levels, compared with the approved drug. This open-label dose-escalation study enrolled prostate cancer patients at the Memorial Sloan-Kettering Cancer Center in New York. Subjects in the initial cohort received escalating doses of GPI-0100 (100ug-3000ug; n=20), with subsequent cohorts receiving higher doses (1000ug-5000ug) of a more purified formulation of the drug (n=14) or 100 ug of the competitive saponin adjuvant QS-21 (n=9).
February 22, 2005
Aphton announced negative results of a phase III study of Insegia (G17DT immunogen) in combination with gemcitabine chemotherapy, for the treatment of pancreatic cancer. Trial data failed to meet their primary efficacy endpoint, with no improvements in overall survival noted versus gemcitabine alone. Survival benefit was noted among the subset of patients who demonstrated antibody response, compared to both the gemcitabine monotherapy arm and those subjects receiving Insegia not demonstrating antibody response. No significant difference in the incidence of adverse events was noted. This randomized study enrolled 383 patients with treatment-naïve pancreatic cancer, who received either combination therapy with Insegia and gemcitabine or gemcitabine alone. The company announced that it hoped to use these results in the design of future trials, and in support of a planned phase III Insegia monotherapy trial in chemotherapy intolerant patients.
Dendreon announced positive results of a phase III study of Provenge (APC-8015), their investigational immunotherapy for the treatment of prostate cancer. Patients receiving the drug experienced a significant 4.5-month improvement in median survival time, vs. placebo (25.9 months vs. 21.4 months, p=0.01). This marks the largest median improvement in survival time in this patient population for any therapy. Efficacy was also noted in promoting survival through 36 months, with 34% of Provenge patients reaching this mark vs. 11% for placebo (p=0.0046). This double-blind, placebo-controlled trial randomized 127 men with asymptomatic, metastatic androgen independent prostate cancer to receive 3 infusions of Provenge or placebo over 4 weeks.
Point Therapeutics reported positive interim results from a phase II trial of talabostat (PT-100), their dipeptidyl peptidase inhibitor for the treatment of metastatic melanoma. Data collected from the first 10 patients yielded preliminary evidence of efficacy, with 1 patient who had previously failed treatment with IL-2 experiencing a partial tumor response (reduction in tumor size of at least 30%). Achievement of this milestone allows the continued accrual of patients. This open-label, single arm study was designed to enroll a total of 30 patients with metastatic melanoma, who were to receive up to 6 cycles of talabostat monotherapy, with oral administration once daily for 14 days, followed by a 7 day washout. The company announced that these results, along with those from other phase II studies, would be used to establish proof-of-principle for talabostat.
November 1, 2004
Bayer Pharmaceuticals and Onyx Pharmaceuticals announced results from a phase II study of BAY 43-9006, for the treatment of advanced kidney cancer. Trial data met their primary endpoint, with a significantly higher portion of patients receiving BAY 43-9006 maintaining a stable disease state versus subjects receiving placebo. Overall, 70% of study participants receiving the drug demonstrated stable disease state or tumor shrinkage. This multi-center, two-stage, multi-cohort discontinuation trial enrolled a total of 502 subjects, 202 of which had advanced kidney cancer; all subjects received BAY 43-9006 for 12 weeks. Subjects demonstrating stable or similar disease states progressed into a 12 week, placebo-controlled, randomized investigation, while patients showing significant response to the drug entered a parallel open-label phase. The companies announced that the data from this trial would support their ongoing phase III study, which, if successful, would set the likely approval date in 2006.
Cougar Biotechnology announced the combined results of three phase I trials of their investigational drug CB7630 (abiraterone), for the treatment of hormone refractory prostate cancer. Data from all three studies demonstrated preliminary efficacy, achieving significant reductions in serum testosterone levels in two single-dose trials and in one multiple-dose trial. Furthermore, the highest dose in the multiple dose trial suppressed testosterone levels to those comparable to those observed in patients on leutenizing-hormone releasing hormone (LHRH) agonists (>0.7 nmol/L). All three trials investigated dose-ranging regimens of the drug in castrate and non-castrate hormone refractory prostate cancer patients at a single center in the UK; two of the trials investigated single escalating doses, and the third utilized one of two 12 day, dosing regimens.
Peregrine Pharmaceuticals reported positive results of a phase I study of Cotara, their radio-conjugated monoclonal antibody for the treatment of colorectal cancer. The trial found the drug to be safe and well tolerated, with bone-marrow suppression observed as the most frequent dose limiting toxicity, as anticipated. In addition, though no incidence of objective response was noted following single-dose administration, tumor targeting was confirmed via radioimaging, and radiation absorption was much higher in tumor tissue than surrounding organs. This single-agent, single-dose, dose escalating study enrolled patients with advanced refractory colorectal cancer. The company announced that it was working to devise further trials to investigate the drug both as a single agent and adjuvant to other therapies.<
July 26, 2004
GTx has reported new data from their successful Phase IIb study of Acapodene (toremifene citrate), for the prevention of prostate cancer in high risk men. Data indicated that a one year Acapodene regimen was efficacious in reducing the risk of cancer onset, with a 24.4% risk of onset, compared with a 31.2% risk in placebo subjects. Furthermore, it was noted that subjects who showed a negative biopsy at 6 months remained cancer free more often at 12 months, with a 48% risk reduction noted. Subjects who did develop prostate cancer while on the drug demonstrated a statistically similar tumor severity, with a trend towards reduction. This double blind, placebo controlled study enrolled 514 men with high grade prostatic intraepithelial neoplasia, a risk factor for prostate cancer. Adverse events were similar to placebo, and included headache, fatigue, hot flashes, and nausea.
July 12, 2004
Celgene has published positive results of a phase II trial of Thalomid (thalidomide), in combination with docetaxel (taxotere), for the treatment of metastatic androgen-independent prostate cancer (AIPC). Thalomid is currently approved for the treatment of leprosy. Data from the trial indicated that the addition of Thalomid to standard docetaxel therapy produced both significant and non significant improvements in several disease measures. The trial enrolled 75 prostate cancer patients, all of whom received docetaxel infusions once weekly for 3 of 4 weeks; 50 subjects were also treated daily with orally administered Thalomid. Addition of Thalomid produced significant increases in the number of patients who experienced a greater-than-50%-reduction in prostate-specific antigen levels, and in median overall survival time. Non-significant improvements were seen in 18-month survival rates (68.2% vs. 42.9%, p=0.11) and median progression free survival time (5.9 months vs. 3.7 months, p=0.32). Celgene announced plans to continue clinical development of Thalomid for this indication.
Cell Genesys has reported positive initial results of their phase II trial of GVAX, their anti-cancer vaccine therapy, for the treatment of inoperable, treatment-refractory metastatic pancreatic cancer. Trial data have indicated that the vaccine may be effective in improving survival time and promoting stable disease state, even in this difficult to treat population. 50 subjects, the majority of whom had failed at least two regimens of chemotherapy, were treated with up to 6 doses of the GVAX vaccine; 20 of these subjects also received low doses of the chemotherapeutic cyclophosphamide, at sub-therapeutic levels associated with generating an immune response. The group receiving the combination of drugs demonstrated trends towards improvement in disease stability, median time to progression and median survival time, compared with GVAX alone. A second phase II trial of GVAX, in patients with operable pancreatic cancer, is ongoing, with results expected during 2005.
March 1, 2004
Procyon Biopharma reported additional positive results from an ongoing phase IIa trial investigating PCK3145, a therapeutic peptide for the treatment of metastatic hormone-refractory prostate cancer. Results confirmed Prostate Specific Antigen (PSA) reduction or stabilization in nine subjects and reduction or normalization of plasma Matrix metalloproteinase 9 (MMP-9) in all subjects. The study was designed with four cohorts of four subjects each and was conducted in the U.K. Subjects received 5, 20, 40 and 80 mg/m2 intravenous doses, three times a week for 4 weeks followed by a seven day observation period. The primary objective is the safety and the tolerability of PCK3145, with secondary objectives of efficacy data, tumor response and hormone levels. The company expects to disclose final results study during Q2 2004.
Stressgen reported results from two clinical trials investigating HspE7, an immunotherapeutic product for the treatments of recurrent respiratory papillomatosis (RRP) and anal dysplasia. Results from the phase II RRP study showed high statistical significance in the lengthening the interval between surgeries, its primary endpoint. Data demonstrated that the median of all post-treatment inter-surgical intervals increased 107.6 days compared to 55.3 days at baseline, a 95% increase. The single arm, open label trial enrolled 27 pediatric subjects. Results from the anal dysplasia trial showed the study did not meet its primary end point of measured adjudicated pathological assessment of biopsies. Secondary endpoints of physician's global assessment and a subset of patients with concomitant genital warts reached statistical significance. The study enrolled 133 subjects with anal dysplasia.
October 13, 2003
American Pharmaceutical Partners and American BioScience reported positive results from a phase III trial investigating Abraxane (ABI-007), a nanoparticle albumin-bound paclitaxel for the treatment of metastatic breast cancer. Results demonstrated that Abraxane achieved higher anti-tumor activity and less toxicity than Taxol. Data showed a higher tumor response rate and a longer time to tumor progression in subjects receiving Abraxane. In addition, a secondary analysis showed the target lesion response rate was found to be significantly higher with Abraxane compared to Taxol. Both treatment regimens were well tolerated. The pivotal, randomized, controlled trial study enrolled 460 subjects and was designed to compare the safety and efficacy of Abraxane to Taxol, administered every three weeks. The dose of paclitaxel (260 mg/m2) was approximately 50% higher than that in the Taxol arm (175 mg/m2).
Hybridon reported positive results from a phase I trial investigating GEM 231, an antisense oligonucleotide for the treatment of solid tumors. Results showed low-grade fatigue in 57% of subjects that was cumulative over 4-6 weeks of repeated 5-day infusions and that rapidly reversed at the end of treatment. In addition, dose-related, reversible increases in serum transaminases and activated partial thromboplastin times were observed. The study enrolled 14 subjects who received escalating doses of GEM 231 in continuous intravenous infusion at 80 to 180 mg/m2/day. Results were reported in the September 15th issue of Clinical Cancer Research.
Procyon Biopharma reported positive interim results from a phase IIa trial investigating PCK3145, a natural prostate secretory derived protein for the treatment of prostate cancer. Results showed that two out of the four subjects in the first cohort showed a decline in PSA levels following treatment with PCK3145. Two subjects in the second cohort also showed an initial response in PSA reduction. Data also showed that four subjects who had plasma Matrix Metalloproteinase-9 (MMP-9) levels over 100 ug/L before treatment had reductions ranging from 34% to 90% after two cycles of treatment. The study showed no drug-related adverse effects. Results were reported at BioContact, Quebec City, Canada.
September 22, 2003
Dendreon reported mixed preliminary results from a phase III trial investigating Provenge, a recombinant antigen therapy for the treatment of prostate cancer. Data showed that subjects in the Provenge group did not reach statistical significance in the primary endpoint of the study, a delay in time to disease progression, as measured by the Kaplan-Meier method. Results of survival data showed a median survival of 26.3 months in the subjects taking Provenge compared with 19.3 months with placebo. The randomized, double blind, placebo controlled study enrolled 167 men and was designed to measure time to disease progression and time to development of disease-related pain in subjects with androgen independent prostate cancer. Final survival data from D9901 is anticipated to be available in late 2004 to early 2005.
Genta and Aventis reported positive results from a phase III trial investigating Genasense (oblimersen sodium) plus chemotherapy for the treatment of malignant melanoma. Results showed that the addition of Genasense to dacarbazine resulted in a median survival of 9.1 months, compared with 7.9 months for subjects treated with dacarbazine alone. Subjects treated with Genasense plus dacarbazine achieved an antitumor response rate of 11.7% (using RECIST criteria), compared with 6.8% with dacarbazine alone. The randomized study enrolled 771 chemotherapy naïve subjects at 140 sites from 12 countries. The primary endpoint was to compare the overall survival between the two treatment arms. Secondary endpoints included comparative analyses of progression-free survival and tumor response.
July 7, 2003
GTX reported positive results from a phase II trial investigating Acapodene (toremifene), a non-steroidal estrogen modulator for the treatment of neoplasia. Results showed the drug was well tolerated and significantly reduced high grade prostate intraepithelial neoplasia (PIN). Data demonstrated that 72% of men had no PIN and no cancer on subsequent biopsies compared to 17.9% of historical controls. The open-label study enrolled 21 men with evidence of high grade PIN on biopsy within six months of entry to the study. Eighteen men completed treatment with Acapodene (60 mg/day orally for four months) and then underwent follow-up prostate biopsy to determine high-grade PIN status. PINs are premalignant lesions that have the potential to progress to prostrate cancer. Results were presented at the 4th International Symposium on Hormonal Carcinogenesis in Spain.
NeoPharm reported positive results from a phase I trial investigating LErafAON, a liposomal c-raf oligodeoxynucleotide for the treatment of various cancers. Results showed that a 2.0 mg/kg dose given twice weekly appeared to be well tolerated, and detectable rafAON levels were observed in the bloodstream over time. Most drug-related adverse events were infusion-related reactions such as back pain, chills, dyspnea, fatigue, fever, flushing and hypertension. The study enrolled 13 subjects and was designed to determine the maximum tolerated dose and toxicities of intravenous LErafAON in patients with advanced solid tumors receiving palliative radiation therapy. Subjects received treatment followed by radiation daily for 10 days. Results were reported at the American Society of Clinical Oncology (ASCO) 39th Annual Meeting in Chicago.
June 16, 2003
Dendreon reported additional positive results from a phase III trail investigating Provenge, an investigational therapeutic vaccine for the treatment of metastatic prostate cancer. Results showed that Provenge induced a significant T-cell mediated immune response compared with placebo. Data revealed Provenge treated subjects demonstrated an eight-fold increase in T-cell proliferation compared to placebo treated subjects. The double blind, placebo controlled study enrolled men with androgen independent prostate cancer. Provenge treated men, with a Gleason score of seven or less, developed a median change in T-cell mediated immune response seven-fold greater than those seen men with a Gleason score of eight and higher. No apparent benefit from Provenge therapy was observed among subjects with Gleason scores of eight or higher. The score is based on tissue findings throughout the prostate that correlate with the aggressiveness of a tumor.
AltaRex reported positive results from a phase III trial investigating OvaRex (oregovamab), a murine monoclonal antibody for the treatment of ovarian cancer. Results showed the time to relapse was 13.3 months with OvaRex compared with 10.3 months with placebo treatment. Subjects with optimal surgical cyto-reduction and no evidence of disease following chemotherapy showed a dramatic clinical benefit as compared to placebo. Subjects with less favorable response to surgery and chemotherapy did not appear to benefit from OvaRex. The randomized, multi-center, placebo-controlled study enrolled 145 subjects following front-line surgery and chemotherapy for stage III/IV ovarian cancer. The side effect profile for OvaRex treatment was similar to placebo.
Genta reported positive preliminary results from a phase II trial investigating Genasense (oblimersen sodium), a BCl-2 protein inhibitor for the treatment of non-Hodgkin’s lymphoma. Results show that across all Genasense treatment groups, 10 of 25 subjects (40%) remained stable without progression during all six treatment cycles. Out of 16 previously treated subjects, one subject (6%) achieved a complete response, and six subjects (38%) achieved stable disease when receiving Genasense alone. During disease progression subjects who were diagnosed and who had not previously received chemotherapy then received a combination of Genasense plus a standard regimen consisting of Rituxan(R), cyclophosphamide, doxorubicin, vincristine, and prednisone. The ongoing study enrolled 37 subjects with mantle cell lymphoma. So far, 25 subjects are evaluable for response; 14 of these patients are still receiving treatment. The study was designed to evaluate the effects of Genasense used without chemotherapy, given every 3-4 weeks.
Spectrum Pharmaceuticals reported positive results from a phase III trial investigating satraplatin, an oral platinum compound for the treatment of prostate cancer. Results demonstrated statistically significant superiority in time to disease progression with satraplatin and a doubling of progression-free survival. The median time to disease progression was 5.2 months for satraplatin versus 2.5 months for the control arm. Data showed a median overall survival time of 15 months for subjects treated in the satraplatin arm versus 12 months for subjects in the control arm. The randomized study 50 subjects with hormone-refractory prostate cancer and evaluated satraplatin plus prednisone versus prednisone alone for use as a first-line chemotherapy treatment. A greater than 50% decline in PSA (prostate-specific antigen) was experienced by 33% (9/27) of subjects in the satraplatin arm versus 9% (2/23) of subjects in the control arm.
SuperGen reported positive results from a phase III trial investigating Orathecin (rubitecan), a topoisomerase I-inhibitor for the treatment of advanced ovarian cancer. Results showed that 7% (13/196) of subjects given Orathecin experienced either a complete or partial tumor response compared with less than 1% (1/211) for subjects receiving an alternative treatment. The median time to disease progression was 57 days for subjects receiving Orathecin, versus 47 days for subjects receiving alternative. The primary study end-point was overall survival, with secondary end-points of tumor response and time to disease progression. Most of subjects in the alternative treatment group received a chemotherapeutic agent such as gemcitabine, 5-FU, mitomycin C, capecitabine, or docetaxel. The randomized, comparative clinical study enrolled 409 subjects with advanced pancreatic cancer.
April 21, 2003
Oncolytic Biotech reported positive interim results from an ongoing phase II trial investigating Reolysin, a reovirus for the treatment of prostate cancer. Early results showed evidence of viral activity in five of six subjects. Preliminary data also demonstrated clear histopathological evidence of apoptotic tumor cell death in four of the six subjects. In a fifth patient, the PSA level dropped by 53% and the prostate gland shrank by 67% from just prior to treatment to the time of surgical removal. The study is designed to evaluate the histopathological efficacy of Reolysin for the treatment of prostate cancer. The primary efficacy endpoint will be the response rate as measured by pathological examination of the tumor.
March 17, 2003
Praecis Pharmaceuticals reported positive results from a phase III trial investigating Plenaxis (abarelix injection), a testosterone production inhibitor for the treatment of prostate cancer. Results demonstrated that the median time to medical castration was significantly shorter for subjects treated with Plenaxis, compared to subjects treated with Zoladex plus Casodex. The data indicated that overall disease progression rates were similar in both treatment groups (9%) through one year of treatment. In addition, 96% of the subjects treated with Zoladex plus Casodex experienced a testosterone surge, defined as a 10% increase above baseline, compared to 0% of the subjects treated with Plenaxis. The randomized, open label, multicenter study enrolled 177 subjects and was designed to test the efficacy and safety of Plenaxis compared to the typically prescribed combination therapy of Zoladex plus Casodex.
February 18, 2003
Abbott Laboratories reported negative preliminary results from a phase III trial investigating atrasentan (ABT-627), an endothelin-blocking protein for the treatment of metastatic prostate cancer. Results showed that the study did not meet its primary endpoint, time-to-disease progression. The endpoint was defined as the need for pain medication, chemotherapy, radiation, and the progression of cancer in bone. The study showed subject dropout rates that were similar to placebo and were lower than in previous studies. Data showed a statistically significant improvement in prostate-specific antigen (PSA) levels compared to placebo (175 ng/ml vs. 257 ng/ml) and improvements in skeletal progression markers. The double blind, placebo-controlled, multinational study enrolled 810 subjects and was designed to examine the effects of atrasentan in men with advanced metastatic hormone-refractory prostate cancer. The company will continue the development of atrasentan in non-metastatic prostate cancer and other cancers.
Transgene reported positive results from two phase I trials investigating their gene therapy products, Adeno Interferon gamma (Ad-IFNg) and Adeno Interleukin-2 (Ad-IL2) for the treatment of various cancers. Both products showed positive results in gene transfer efficiency and cytokine expression. The results also showed positive clinical responses in tumor regression and stabilizations in cutaneous lymphoma subjects treated with Ad-IFNg. The Ad-IFNg trial enrolled 20 subjects with metastatic melanoma or other advanced solid tumors. The Ad-IL2 trial enrolled nine subjects with primary cutaneous T-cell lymphoma and multilesional cutaneous B-cell lymphoma. Treatments were well tolerated in both studies with only mild injection site reactions reported.
February 3, 2003
Active Biotech reported positive preliminary results from a phase I trial investigating TASQ (Tumor Angiogenesis Suppression by Quinolines) for the treatment of prostate cancer. The study shows that the candidate drug has absorption properties that make it well suitable for oral administration. The study was designed to study the pharmacokinetic characteristics of the drug in healthy subjects. Active Biotech expects to initiate more clinical trials of TASQ in the spring of 2003.
December 9, 2002
Advanced Magnetics and Cytogen reported positive results from a phase III trial investigating Combidex, an investigational contrast agent for use with magnetic resonance imaging (MRI). The study showed that Combidex is able to distinguish malignant lymph nodes from normal ones in a variety of cancers. In one part of the study, 50 subjects with primary prostate cancer who were scheduled for radical prostatectomy were given an MRI. Using Combidex, the analysis detected malignant lymph nodes with 93% specificity and 92% sensitivity, indicating a high level of correlation. In another part of the study, 12 subjects with renal cancer who were scheduled for radical nephrectomy were given an MRI. Using Combidex, the analysis detected malignant lymph nodes with 86.6% sensitivity and 96.9% specificity, resulting in a positive predictive value of 76.4% and a negative predictive value of 98.4%. Lymph node status is essential for determining the most appropriate strategy in cancer treatment.
Vasogen reported positive results from a phase II trial investigating their immune modulation therapy, an inflammation suppressor for the treatment of chronic lymphocytic leukemia. More than 60% of the treatment subjects in the optimal dose group reached the primary end-point, which was a 25% reduction in total tumor burden or a greater than 25% reduction in lymph node size compared to baseline. The open-label pilot study enrolled 18 subjects with chronic lymphocytic leukemia who were treated in three groups of six subjects each. The study showed the therapy was well tolerated with no treatment related adverse events.
September 30, 2002
Positive results were reported from a phase II trial of Dendreon's Provenge. In the study, 82 of the 127 subjects with metastatic hormone resistant prostate cancer were treated with Provenge. The results demonstrated that subjects with hormone resistant prostate cancer who have a Gleason score of seven or less significantly benefited from treatment with Provenge. The median time to disease progression for the Provenge group was 16 weeks compared to nine weeks for the placebo group. In addition, there was a greater than eight-fold advantage in progression-free survival of subjects whose disease had not progressed six months after randomization, compared to subjects whom received placebo.
August 19, 2002
While the primary endpoint was not met in a phase III trial of Provenge, an investigational vaccine for the treatment of late-stage prostate cancer, preliminary analyses showed some favorable results. The randomized, placebo-controlled study, which involved 127 subjects with late-stage, metastatic, hormone-resistant prostate cancer, evaluated the time to objective disease progression as its primary endpoint. The clinical benefit in the 82 subjects treated with Provenge approached, but did not achieve, the pre-specified primary endpoint when compared to placebo. Investigators were encouraged, however, by the fact that there was a statistically significant correlation between the subjects' Gleason scores and their therapeutic response to Provenge. Subjects with Gleason scores less than or equal to 7 had a median time to disease progression of 16 weeks, compared to nine weeks for the placebo group. Since approximately 75% of hormone resistant patients have Gleason scores of 7 or less, these results are promising. Provenge is being developed by Dendreon.
April 8, 2002
Positive results were obtained from a phase I/II trial of Northwest Biotherapeutics' DCVax-Prostate, a dendritic cell-based immunotherapy. Data from 31 late-state prostate cancer subjects with no other treatment alternatives showed that 54.8% (17 of 31) experienced overall stabilization of disease. Twelve of the subjects, each of whom had rising PSA values following hormone therapy, did not have measurable metastatic disease at the time of treatment initiation. As measured by radiographic criteria, all 12 subjects were stable at weeks 23 and 28.
December 10, 2001
Positive results were reported from a phase I trial of Inhale Therapeutic Systems' inhaleable leuprolide, a peptide analog used to treat prostate cancer and endometriosis. Data showed that a powdered formulation of leuprolide developed with Inhale's Inhance pulmonary delivery technology administered the drug with a bioavailability of 18% (inhaleable versus injectable systemic delivery). In the 12-subject trial, the powdered leuprolide dose was packaged in a single capsule, and subjects inhaled the drug using a small dry powder inhaler.
The final results from a phase IIb trial of Valentis' interleukin-2 (IL-2) GeneMedicine product did not confirm positive interim findings. The randomized trial was designed to compare the IL-2 GeneMedicine product plus standard chemotherapy to standard chemotherapy alone in subjects with advanced head and neck cancer. The trial data demonstrated that the positive trend in the IL-2 treatment group versus the chemotherapy alone group was not sustained throughout the trial. The trial was conducted in collaboration with Roche Holdings.