June 12, 2017
Hutchison China MediTech (Chi-Med) announced results from its pivotal phase III trial with fruquintinib in patients with locally advanced or metastatic colorectal cancer (CRC). The FRESCO trial is a randomized, double-blind, placebo-controlled, multicenter trial. Enrollment was completed in May 2016; 519 patients were screened. The intention-to-treat (ITT) population of 416 patients was randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on/one-week-off cycle, plus BSC (278 patients); or placebo plus BSC (138 patients). Randomization was stratified for prior anti-VEGF therapy and K-Ras gene status. The primary endpoint of median overall survival (OS) was 9.30 months [95% CI 8.18–10.45] in the fruquintinib group vs. 6.57 months [95% CI 5.88–8.11] in the placebo group, with a hazard ratio of 0.65 [95% CI: 0.51–0.83; two-sided p<0.001]. The secondary endpoint of median progression-free survival (PFS) was 3.71 months [95% CI 3.65–4.63] in the fruquintinib group vs. 1.84 months [95% CI 1.81–1.84] in the placebo group, with a hazard ratio of 0.26 [95% CI: 0.21–0.34; two-sided p<0.001]. Chi-Med expects to complete the New Drug Application (NDA) submission for fruquintinib to the China Food and Drug Administration imminently. The company also expects to initiate U.S. clinical studies in 2017.
June 13, 2016
Array BioPharma released results of a phase II trial of encorafenib for BRAF-mutant colorectal cancer. In the phase II trial, 102 patients were randomized 1:1 to receive encorafenib and cetuximab with or without alpelisib. Median PFS was 5.4 months and 4.2 months for the triplet and doublet regimens, respectively. An early analysis of median OS exceeded one year for the triplet regimen and was not reached for the doublet regimen. Confirmed ORR was 27% (95% CI, 16-41%) for the triplet regimen and 22% (95% CI, 12-36%) for the doublet regimen. Grade 3/4 AEs occurring in greater than 10% of patients in either arm included anemia, hyperglycemia and increased lipase. Historical published PFS and OS results after first-line treatment range between 1.8 to 2.5 months and four to six months, respectively, and published response rates from various studies in this population range between 6% to 8%.
January 18, 2016
Sorrento Therapeutics reported results
of a phase III study of STI-001 in China for
epidermal growth factor receptor (EGFR)
expressing metastatic colorectal carcinoma
patients. STI-001 was used in combination
with irinotecan versus irinotecan alone. The
combination therapy showed significant
improvement compared to chemotherapy
alone in overall response rate (ORR: 32.9% v.
12.8%) and progress-free survival (PFS: 5.6 v.
3.2 months) as well as longer overall survival
(OS: 14.1 v. 13.4 months). The ORR, PFS and
OS using STI-001 and irinotecan are increased
significantly than previously reported in
similar medical settings using Erbitux and
irinotecan (32.9% v. 10%; 5.6 v. 4 months;
14.1 v. 11.6 months). During the 501-patient,
double-blind, randomized trial, STI-001 was
well-tolerated. Adverse events (AEs), especially
grade three and four AEs, were found to
be significantly fewer than those previously
reported using Erbitux. While it was reported
that more than 10% of patients using Erbitux
showed hypersensitive reaction (grade three/
four), none was recorded in the completed
phase III study of STI-001.
February 2, 2015
PharmaEngine released results of a phase II
study of PEP02 (MM-398, liposome irinotecan
injection) in unresectable metastatic colorectal
cancer (mCRC). The PEPCOL study evaluated
the efficacy and safety of PEP02 (MM-398) in
combination with 5-FU/LV (FUPEP regimen)
or irinotecan plus 5-FU/LV (FOLFIRI regimens:
FOLFIRI-1 or modified FOLFIRI-3) as a secondline
therapy in patients with mCRC. The primary
endpoint was the objective response rate (ORR).
Fifty-five patients were randomized (FUPEP,
n=28; FOLFIRI, n=27) and non-comparative randomly
assigned to FUPEP (PEP02 80mg/m² d1,
folinic acid (FA) 400mg/m² d1, 5-FU 2,400mg/m²
d1-2) or FOLFIRI (FOLFIRI-1: irinotecan 180mg/
m² d1, FA 400mg/m² d1, 5-FU bolus 400mg/m²
d1, 5-FU infusion 2,400mg/m² d1-2; or modified
FOLFIRI-3: irinotecan 90mg/m² d1 and 3,
FA 400mg/m² d1, 5-FU infusion 2,400mg/m²
d1-2). Bevacizumab q2w (5mg/kg) was allowed
in both arms as of June 2012. In the intent to
treat population, the ORR of the FUPEP regimen
was 14% (4/28), which compared favorably with
FOLFIRI-1 (0%, 0/10) and was comparable to the
modified FOLFIRI-3 regimen (18%, 3/17). Most
common grade 3-4 adverse events reported in
the respective FUPEP and the FOLFIRI arms were
neutropenia (11% v. 30%) and diarrhea (21% v.
33%), which were numerically lower in the FUPEP
arm than in the FOLFIRI arm; other aspects
of the safety profiles were similar between the
two arms. Based on the acceptable safety profile
of the FUPEP regimen in this PEPCOL study,
it was added as the third arm to the phase III
metastatic pancreatic cancer (NAPOLI-1) study in
which this FUPEP regimen (MM-398 + 5-FU/LV
arm) met the primary endpoint of a statistically
significant improvement in overall survival.
July 14, 2014
Taiho Oncology issued results of a
phase III trial of TAS-102 (trifluridine
and tipiracil hydrochloride) for the treatment
of refractory metastatic colorectal
cancer. The trial was a global, randomized,
double-blind, placebo-controlled comparison
trial. The trial enrolled 800 patients in
North America, Japan, Europe and Australia
who received at least two prior regimens
of standard chemotherapies for mCRC and
were refractory to, or failed, those chemotherapies.
Patients were randomized (2:1)
to receive TAS-102 (35mg/m2) or placebo,
plus best supportive care, twice daily.
The trial met the primary efficacy endpoint
of statistically significant improvement in
overall survival versus placebo (H =0.68,
p<0.0001). TAS-102 reduced the risk of
mortality by 32% when compared to
placebo. Median overall survival was 7.1
months (95% CI: 6.5-7.8) and 5.3 months
(95% CI: 4.6-6.0) for TAS-102 and placebo,
respectively, and was improved in favor
of TAS-102 by 1.8 months. There also was
a statistically significant 52% decrease in
the risk of disease progression between
the two arms (HR=0.48, p<0.0001). In
addition, the disease control rate of
patients treated with TAS-102 was 44.0%
versus 16.3% for patients treated with
placebo (p<0.0001). Taiho plans to submit
regulatory submissions in the U.S. at the
end of 2014 and in Europe in the first
quarter of 2015.
May 13, 2013
Amgen issued results from a phase III head-to-head trial of Vectibix (panitumumab) versus Erbitux (cetuximab) for chemorefractory metastatic colorectal cancer (mCRC). This global, randomized, parallel-assignment, open-label, non-inferiority study enrolled 1,010 patients with mCRC with wild-type KRAS tumors. Subjects received 6mg/kg of intravenous Vectibix every 14 days or 400mg/m2 of an initial dose of intravenous Erbitux followed by 250mg/m2 of intravenous Erbitux every seven days. Data demonstrated the estimated overall survival hazard ratio (Vectibix/Erbitux) was 0.966 (95% CI: 0.839, 1.113) favoring the Vectibix arm. Vectibix was well tolerated. Overall, the relative adverse event profiles were as anticipated for each of the anti-EGFR therapies studied, including known events such as rash, diarrhea and hypomagnesemia.
February 4, 2013
Amgen issued results from a phase III trial of Neulasta (pegfilgrastim) for the treatment of colorectal cancer. This multinational, randomized, double-blind, placebo-controlled trial enrolled 845 patients receiving FOLFOX or FOLFIRI and bevacizumab for the first-line treatment of locally-advanced or metastatic colorectal cancer. Subjects received 6mg of Neulasta, or placebo, at least 24 hours after each cycle of chemotherapy. Results showed the study met its primary endpoint: Neulasta significantly reduced the incidence of febrile neutropenia (low white blood cell count accompanied by a fever). In the study, the incidence of grade 3 or 4 febrile neutropenia in patients receiving Neulasta across the first four cycles of chemotherapy was 2.4%, compared to 5.7% in the placebo group (OR=0.41, p=0.014). A similar incidence of grade 3 or higher adverse events was seen in both arms of the trial (28% placebo; 27% Neulasta). The drug was well tolerated. Amgen did not note its plans for Neulasta.
January 30, 2012
Immatics reported results from a phase I/II trial of IMA910, a therapeutic vaccine under development for the treatment of colorectal cancer. This single-arm, open label study enrolled 92 subjects with advanced colorectal cancer who had successfully completed a 12-week first-line treatment with oxaliplatin-based chemotherapy. The subjects were vaccinated with IMA910 plus a GM-CSF adjuvant up to 16 times over a period of nine months. IMA910 was able to stimulate relevant immune responses against the tumor-associated peptides (TUMAPS) in the majority of subjects. In the subjects who had detectable T cell responses against two or more of the TUMAPS contained in IMA910, a consistently better clinical outcome (disease control, progression-free survival and overall survival) was observed compared to those who did not have a detectable multi-T-cell response. In addition, subjects who mounted both CD8+ and CD4+ multi-T-cell responses did not reach the median survival after more than 28 months of follow-up compared to a 16 months median survival time in those who did not (p≡0.088). IMA910 was well tolerated with injection-site reactions being the most frequent side effect.
January 23, 2012
Bayer Healthcare reported results from a phase III trial of regorafenib for the treatment of metastatic colorectal cancer. This international, multicenter, randomized, double-blind, placebo-controlled study, CORRECT, (ColORrectal cancer treated with REgorafenib or plaCebo after failure of standard Therapy), enrolled 760 subjects with metastatic CRC who had progressed after standard therapies. The subjects received regorafenib or placebo plus best supportive care (BSC). Treatment cycles consisted of 160 mg of regorafenib or matching placebo once daily for three weeks with one week off plus BSC. The primary endpoint was reached, with data showing statistically significant improvement in overall survival by 29% (p≡0.0052; median 6.4 months versus 5.0 months for the placebo group). Statistically significant improvements over placebo were also reached in the secondary endpoints of progression-free survival (p<0.000001, median 1.9 months versus 1.7 months) and disease control rate (44.8% versus 15.3%).
May 2, 2011
Sanofi Aventis and Regeneron released initial results from a phase III trial of Zaltrap for the second-line treatment of metastatic colorectal cancer. This multinational, randomized, double-blind trial, VELOUR, enrolled 1,226 subjects who had previously been treated with an oxaliplatin-based regimen. The subjects received Zaltrap in combination with the FOLFIRI chemotherapy regimen [folinic acid (leucovorin), 5-fluorouracil, and irinotecan] or a regimen of FOLFIRI plus placebo. The primary endpoint, improvement of overall survival, was reached.
January 31, 2011
ArQule issued interim results from an ongoing phase I/II trial of ARQ-197 for colorectal cancer. This trial was designed to compare the combination of ARQ-197 with irinotecan and cetuximab in patients with metastatic colorectal cancer with the wild-type form of the KRAS gene. The combination was well tolerated and demonstrated anti-tumor activity. Among nine treated subjects, one had a complete response, two had partial responses and five subjects had stable disease. The phase II portion of the trial is now underway. Enrollment will include approximately 150 subjects with the wild-type form of the KRAS gene who have received front-line systemic therapy. No dose limiting toxicities were observed.
August 23, 2010
Positive results were reported from a phase II trial evaluating Sirtexs SIR-Spheres for the treatment of colorectal cancer liver metastases. This single arm trial enrolled 52 subjects with metastatic colorectal cancer who had failed prior chemotherapy regimens containing oxaliplatin and irinotecan. The SIR-Spheres were injected into the artery supplying blood to the tumors where they delivered radiation for approximately 14 days. Liver tumors completely disappeared in one subject, and 11 subjects had a partial response involving at least a 30% reduction in tumor size (p≡0.05). An additional 12 subjects had stable disease. The median overall survival for the entire population was 12.6 months, with significantly longer survival in the 24 (48%) subjects that responded to SIR-Spheres or who had stable disease compared to non-responders (median 16 months versus 8 months; p≡0.0006). In addition, 40% of the responders remain alive at two years compared to none of the non-responders. The most commonly reported side effects were fever and pain.
July 12, 2010
Biothera released positive results from a phase Ib/IIa trial of Imprime PGG, an immunotherapy for the treatment of metastatic colorectal cancer. This open label study enrolled second- and third-line colorectal cancer patients and consisted of two arms. The first arm assessed the safety and efficacy of various dose levels of Imprime PGG in combination with Erbitux (cetuximab) and Camptosar (irinotecan), standard of care. Ten subjects were enrolled and dosed with 2, 4 or 6 mg/kg of Imprime PGG in combination with standard doses of irinotecan and cetuximab. Median progression-free survival increased 38% to 22 weeks with the Imprime PGG combination, compared with 16 weeks for the standard of care. The overall response rate (complete response + partial response) was 30% with the Imprime PGG combination, compared to 16% for the standard of care. The disease control rate (complete response + partial response + stable disease) was 100% for the Imprime PGG group, compared with 61% for the standard of care. The second arm assessed Imprime PGG plus cetuximab. This arm enrolled 22 subjects who received 2, 4 or 6 mg/kg of Imprime PGG in combination with standard doses of cetuximab. Data were compared to historical control evaluating cetuximab alone. The median progression free survival was 12 weeks for Imprime PGG plus cetuximab versus six weeks for historical control. The overall response rate was 24% versus 11% and the disease control rate was 62% versus 33%, respectively.
February 22, 2010
Merck issued positive results from a phase III study of Gardasil for the prevention of anal intraepithelial neoplasia (AIN) and anal cancer associated with HPV types 6, 11, 16 and 18. This randomized, double-blind, placebo-controlled trial enrolled 598 males, 16-to-26 years old, who were sexually active with other men. The subjects received at least one dose of the Gardasil or placebo at the time of enrollment, and then again at two and six months. The cases of AIN and anal cancer were counted starting after month seven with an average follow up of 2.5 years. Gardasil prevented 77.5% of HPV 6, 11, 16, and 18-related AIN and anal cancer. A total of 29 subjects were diagnosed with HPV 6, 11, 16 or 18-related AIN during the study, with 24 cases in the placebo group and five in the vaccine group. No cases of HPV 11 or 18-related AIN were observed in the vaccine group. No cases of anal cancer were seen in either the placebo or vaccine group.
February 1, 2010
Keryx reported positive results from a phase II trial of perifosine for the treatment of colorectal cancer. This US-based, randomized, double-blind, placebo-controlled study enrolled 38 subjects with 2nd or 3rd line metastatic colon cancer. The trial was designed to compare perifosine in combination with capecitabine (P-CAP) to capecitabine plus placebo (CAP). The subjects received capecitabine (Xeloda; standard of care) at a dose of 825 mg/m2 twice daily (total daily dose of 1650 mg/m2) on days 1-14 every 21 days, plus either perifosine or placebo at 50 mg daily. Treatment continued until disease progression. Of the 38 enrolled subjects, 35 were evaluable for response. The primary endpoints were time to progression (TTP), overall response rate (ORR) and the clinical benefit rate (CBR). The TTP was 28 weeks for the P-CAP group vs. 11 weeks for the CAP group (p≡0.0012). The P-CAP arm demonstrated a statistically significant advantage for percentage of subjects achieving Stable Disease lasting 12 or more weeks (SD) or better, as compared to the CAP arm (75% vs. 40%; p≡0.036). The ORR was 20% in the P-CAP arm versus 7% in the CAP arm. In addition, the P-CAP arm demonstrated a greater than 60% improvement in median Overall Survival (OS) (18 months vs. 11 months; p≡0.0136).
August 24, 2009
Amgen reported mixed results from a phase III trial evaluating Vectibix in combination with FOLFIRI as a second-line treatment for metastatic colorectal cancer (mCRC). This global, multicenter, randomized, double-blind, placebo-controlled trial, dubbed 181, enrolled 1,186 subjects who were randomized to receive either 6.0 mg/kg of Vectibix and FOLFIRI or FOLFIRI alone every two weeks. The primary endpoints were progression-free and overall survival. Vectibix significantly improved progression-free survival in combination with FOLFIRI, compared to FOLFIRI alone, in patients with KRAS wild-type mCRC. Although numerically greater, the improvement in median overall survival did not achieve statistical significance in the Vectibix arm. The addition of Vectibix had no positive or negative effect on progression-free or overall survival in patients with tumors harboring activating KRAS mutations. There were no unexpected adverse events.
July 21, 2008
Roche issued positive results from a phase III trial of Avastin for the treatment of colorectal cancer. This randomized, controlled study, dubbed AVF2107, enrolled 800 previously untreated subjects with metastatic colorectal cancer. The subjects received Avastin combined with the standard chemotherapy, irinotecan, fluorouracil and leucovorin (IFL) or chemotherapy alone. In a group of subjects with the normal K-Ras gene (wild type), the addition of Avastin led to an 82% increase in progression free survival over chemotherapy alone (7.4 months versus 13.5 months, respectively) as well as a 57% increase in overall survival (17.6 versus 27.7 months, respectively). A significant increase in response rate was also observed; 60% compared to 37% in subjects receiving chemotherapy alone. In a group of subjects with K-Ras mutation, the addition of Avastin led to a 69% increase in progression free survival over chemotherapy alone (5.5 months versus 9.4 months, respectively). Several additional trials of Avastin are currently underway.
June 9, 2008
Celator released positive results from a phase II trial of CPX-1 for the treatment of colorectal cancer. This multi-center, open-label study enrolled 59 subjects who were placed in two arms: irinotecan-naive (IRI-naive) and irinotecan-refractory (IRI-refractory) and received 210 units/m2 of CPX-1 every two weeks. In the IRI-naive arm the overall response rate was 8% and the disease control rate (response or stable disease) was 65 percent. Median progression- free survival (PFS) was 3.9 months and six subjects had a greater than six month PFS. In the IRI-refractory arm the disease control rate was 45%; there were no reports of an objective response. The median PFS was 2.3 months and three subjects had a greater than six month PFS. The 210 unit/m2 dose produced more toxicities than seen in previous phase 1 studies, resulting in only 40 percent of the subjects receiving more than 80 percent of the planned dose intensity. Hence, treatment will be initiated at a lower dose in future studies. Based on the results Celator plans to move forward with the development of CPX-1.
February 4, 2008
Bayer and Onyx released positive results from an ongoing phase I/II trial of sorafenib for the treatment of acute myeloid leukemia (AML). This trial enrolled newly relapsed subjects and those newly diagnosed with high-risk disease. The subjects received sorafenib in combination with the standard of care chemotherapy combination for AML, idarubicin and cytosine arabinoside. Results showed that sorafenib targeted the FLT3-ITD mutation, a genetic mutation active in about one third of the subjects with AML. In sixteen evaluable subjects with this mutation, sorafenib reduced the median percentage of leukemia cells circulating in the blood from 81% to 7.5% and in the bone marrow from 75.5% to 34%. In addition, two subjects had circulating leukemia cells, or blasts, drop to zero. Treatment was well tolerated to date and the maximum tolerated dose has not been reached. Based on the results the trial will continue as planned.
Pro-Pharmaceuticals reported positive results from a phase II trial of Davant for the treatment of colorectal cancer. This trial enrolled twenty previously heavily treated subjects, all of whom had at least two previous chemotherapy treatments including; fluorpyrimidines, Irinotecan, Oxaliplatin and Avastin or Erbitux. All subjects received Davant (280 mg/m2) in combination with 5-fluorouracil (5-FU, 500 mg/m2), given four times monthly until disease progression or unacceptable toxicity. The median progression free survival was 8.4 weeks and one subject reported an objective response. Treatment was generally well tolerated. There were seven reports of serious adverse events, however only two of these, anemia and dehydration, were considered to be drug related. Based on the results, Pro-Pharmaceuticals plans to move forward with the development of Davant.
Wilex released positive results from a phase I trial of WX-UK1 for the treatment of solid tumors. This dose escalation study enrolled twenty five subjects who received once weekly infusions of WX-UK1 for three weeks at various fixed doses and daily capecitabine (Xeloda) concomitantly for two weeks. This three-week cycle was repeated until disease progression or toxicity, or for a maximum of fifteen treatment cycles. Treatment was safe and well tolerated, with no increase in adverse events and no reported serious adverse events. Pharmacokinetic analysis showed no significant reciprocal drug-drug interactions. WX-UK1 showed dose-linear pharmacokinetic profile over the dose range tested. Preliminary efficacy data revealed prolonged stable disease and partial response in several of the subjects. Based on the results, Wilex plans to continue the development of WX-UK1.
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.
October 15, 2007
Adventrx issued negative results from a phase IIb trial of CoFactor for the treatment of colorectal cancer. This open-label, randomized, controlled study enrolled 300 subjects who received CoFactor/5-fluorouracil (5-FU) or leucovorin/5- FU. The primary endpoint was a reduction in the proportion of subjects reporting at least one hematological or gastrointestinal adverse event of grade 3 or greater. The CoFactor/5-FU arm demonstrated comparable overall safety to the leucovorin/5-FU arm. However, the CoFactor/5-FU arm did not demonstrate statistically significant improved safety in the primary endpoint. In addition, no statistically significant differences were observed in overall safety and efficacy variables between the two arms. Adventrx plans to fully analyze the data in order to determine the future course of development of CoFactor for this indication.
Cell Therapeutics announced positive results from a phase I trial of brostallicin for the treatment of advanced solid tumors. This multicenter, dose-escalation trial enrolled 21 subjects who received brostallicin, escalated from 5 to 7 to 9 mg/m2 in combination with a fixed dose of cisplatin (75 mg/m2). Treatment cycles were three weeks. The primary objective was to determine any dose limiting toxicities (DLT) during the first cycle and to define the optimal dose for future studies. No DLTs occurred at the 5 or 7 mg/m2 dose, while two subjects experienced DLTs at the 9 mg/m2 dose. Hence, the optimal dose for upcoming phase II trials was determined to be brostallicin 7 mg/m2 and cisplatin 75 mg/m2 every three weeks. In addition, of the 21 treated subjects, 14 experienced disease stabilization with 7 subjects experiencing disease stabilization for more than 18 weeks. Based on the results, phase II trials are expected to commence shortly.
August 13, 2007
Oxford BioMedica reported positive results from a phase II trial of TroVax for the treatment of metastatic colorectal cancer. This trial was designed to evaluate the safety and immunogenicity of TroVax when administered with chemotherapy. The trial enrolled 17 subjects who received the vaccine before, during and after the standard chemotherapy regimen FOLFOX. A course of treatment consisted of six vaccinations. Throughout the study, subjects were monitored for an immune response to 5T4. Eleven of the 17 subjects who had completed a course of treatment mounted a strong immune response to 5T4. Of these 11 subjects, six showed significant tumor shrinkage and one no longer had any detectable tumors. The overall median survival was 68 weeks in all 17 vaccinated subjects and 118 weeks in the 11 subjects who received all six vaccinations. Additional phase II and III trials are ongoing at this time.
June 4, 2007
Alchemia released positive final results from a phase II trial of HyCAMP for the treatment of colorectal cancer. This randomized trial enrolled 80 subjects with metastatic colorectal cancer who had previously failed therapy with 5 FU. Subjects received up to eight cycles of irinotecan (Camptosar) or HyCAMP intravenously. The results concluded that when compared to the irinotecan arm, the subjects receiving HyCAMP: showed a significantly greater increase in tumor response, showed a statistically significant increase in 'time to treatment failure', had a significantly longer period (+116%) of 'progression-free survival', were able to receive therapy for a median of three times longer than those receiving Camptosar, showed a trend towards longer overall survival and received less doses of anti-diarrheal medication. Based on the results, Alchemia plans to meet with the FDA and EMEA to determine the best future course of action towards gaining approval.
Peregrine announced positive results from a phase Ib trial of bavituximab for the treatment of cancer. This open-label trial enrolled 12 subjects in India who received bavituximab given with standard chemotherapy (including docetaxel, gemcitabine and carboplatin/paclitaxel) over an eight week period. The primary endpoints were safety and tolerability as well as preliminary efficacy. Treatment was generally well tolerated, with a safety profile similar to that seen in advanced cancer patients undergoing chemotherapy alone. Objective tumor response or stable disease occurred in 50% of the subjects evaluable for tumor response. This response was greater In the subjects receiving bavituximab in combination with gemcitabine, with 75% of the subjects showing objective tumor response or stable disease. Based on the results, Peregrine plans to initiate further efficacy trials later in 2007.
May 21, 2007
Pro-Pharmaceuticals released positive interim results from two phase II trials of Davant-1 for the treatment of colorectal and billiary cancer. The primary endpoints for both trials are tumor shrinkage and progression-free survival. The open-label colorectal trial has dosed 8 subjects to date with Davant-1 in combination with 5-FU in a regimen with Avastin and leucovorin. Of these 8 subjects, 7 have stable disease and 2 have evidence of tumor shrinkage, with 40% and 15% reductions in size. The open-label biliary cancer trial has dosed 5 subjects to date with Davant-1 in combination with 5-FU. A 35% reduction in tumor size has been observed in one subject. No increase in drug-related toxicity was observed in either trial. Based on the results the Pro-Pharmaceuticals plans to continue enrolling subjects in both trials.
April 9, 2007
NeoPharm released negative results from a phase II trial ofLE-SN38 for the treatment of colorectal cancer. This trial enrolled 54 subjectswho received LE-SN38 via intravenous infusion for 90 minutes every 21 days. Theprimary endpoints included overall tumor response rate, progression-freesurvival and overall survival. Although interim analysis of 21 subjects showeddisease stabilization, the primary tumor response endpoint was not met. Basedon the results, NeoPharm decided to discontinue enrollment in this trial and toreassess the next steps in the development of LE-SN38.
April 2, 2007
Amgen reported negative results from a phase IIIb trial ofVectibix for the treatment of colorectal cancer. This randomized, open-labeltrial, dubbed PACCE (Panitumumab Advanced Colorectal Cancer Evaluation), wasdesigned to evaluate oxaliplatin- and irinotecan-based chemotherapy and Avastinwith and without Vectibix in the first-line treatment of metastatic colorectalcancer. The study enrolled 1,054 subjects in the United States. The primaryendpoint was a 30% improvement in progression free survival and safety. Interimanalysis revealed an increase in grade 3 serious adverse events in Vectibixtreated subjects. In addition there was a statistically significant differencein progression-free survival and overall survival in favor of the control arm.Based on the results, Amgen decided to discontinue Vectibix treatment in thePACCE trial while they reviewed additional analyses of the results.
October 9, 2006
PharmaMar released positive results from a phase II trial of Aplidin for the treatment of renal and colorectal cancer. This multi-centre, open-label, randomized trial enrolled 81 subjects with advanced renal or colorectal cancer who were placed in one of two study arms. Arm A subjects were administered Aplidin at a dose of 5 mg/m2 and arm B subjects were administered Aplidin at a dose of 7 mg/m2, in combination with L-carnitine. Safety profiles demonstrated that Apildin at the higher dose, in the combination formula, resulted in a higher incidence of adverse events. Efficacy data revealed that stable disease lasting more than 12 weeks occurred in 32.4% of the renal cancer subjects and in 24.3% of the colorectal cancer subjects. Based on the data development of Aplidin, at the lower dose of 5 mg/m2, will continue forward.
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.
April 25, 2005
Adventrx Pharmaceuticals reported results of a phase II trial of CoFactor (CH2FH4), in combination with 5- fluorouracil (5-FU), for the treatment of colorectal cancer. Toxicity and pharmacodynamic data indicated a positive toxicity profile based on a laboratory measures. Specifically, administration of CoFactor produced an increase producing increases in RBC folate pool expansion (form a mean baseline score of 533 ng/ml to a score of 1295 ng/ml following weekly dosing), urinary folate excretion (an indication of formaldehyde toxicity) showed a small decrease (from a baseline historical baseline of 5 ug/ml to a post-treatment mean of 3.7 ug/ml). These data support the use of CoFactor in combination with 5-FU to improve efficacy and reduce toxicity. This open-label study enrolled subjects with metastatic colorectal cancer, and was designed to investigate several laboratory measures of the toxicity associated with CoFactor administration and metabolism, in the hopes that the drug in combination with 5-FU will provide better efficacy and reduced toxicity, compared to standard therapy of 5-FU and leucovorin. The company announced that these data would serve to support upcoming phase IIb and III trials in the UK and the US.
Agennix reported positive results of a phase II trial of talactoferrin alpha in combination with chemotherapy, for the first line treatment of non-small cell lung cancer (NSCLC). Results from the study found that the addition of talactoferrin significantly improved overall response rate vs. placebo. Specifically, overall response rate in the prospectively defined evaluable patient group was 47%, vs. 29% for placebo (p= 0.05). The addition of talactoferrin was also well tolerated, with no evidence of increased toxicity. This double-blind, placebo- controlled study enrolled 110 treatment-naïve NSCLC patients, who were randomized 1:1 to receive talactoferrin or placebo, in combination with a standard chemotherapeutic regimen of carboplatin/paclitaxel.
Human Genome Sciences reported positive results of an ongoing phase I trial of their investigational TRAIL-1 monoclonal antibody HGS-ETR1, for the treatment of solid tumors. Trial data met their safety endpoints, with the highest dose acceptably tolerated and a generally mild (Grade 1 or 2) adverse event profile. Pharmacokinetics were proportional to dose, and mean elimination half-life was 17 days. Efficacy was also noted, with 10 instances of stable disease, including one subject who had received 16 treatments with the drug. This open-label, multi-center, dose- escalation trial had enrolled 44 heavily pretreated subjects to date (median prior chemotherapeutic regimens: 6), who received one of 7 IV doses of the drug (0.01, 0.03, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg), once every 14 or 28 days.
Medarex and Bristol-Myers Squibb reported positive results of a phase II study of their investigational two-drug therapy for metastatic melanoma, which includes the anti-CTLA-4 antibody MDX-010 and the gp100 melanoma vaccine MDX-1379. Both trial dosing regimens yielded evidence of efficacy, with 2 complete responses (ongoing through 30 and 31 months) and 2 partial responses (4 months; ongoing through 34 months) in cohort 1, and 3 partial responses (6 months; ongoing through 25 and 26 months) in cohort 2. Serious Grade III/IV adverse events occurred more often in cohort 1 (n=9) than cohort 2 (n=5). This two- armed open-label study enrolled 56 subjects with metastatic melanoma, who received MDX-1379 plus 3.0 mg/kg MDX-010 every 3 weeks (cohort 1; n=29), or MDX-1379 plus an initial 3.0 mg/kg dose of MDX-010, followed by 1.0 mg/kg every 3 weeks (cohort 2; n=27).
March 14, 2005
Adventrx Pharmaceuticals has reported preliminary results of a phase II trial of CoFactor, in combination with 5-fluorouracil, for the treatment of metastatic colorectal carcinoma. Trial results met their primary efficacy endpoint of enhancing response rate, defined as a reduction in tumor size of at least 50%. Additional data, evaluating safety, time-to-tumor-progression and overall survival, were still being collected. This ongoing open-label, single arm, multi-center trial enrolled 48 patients with surgically-unresectable metastatic disease. Treatment of additional patients and data collection are ongoing, and the company plans to present additional data from this study at the 2005 Annual Meeting of the American Society of Clinical Oncology in May.
Medarex and Bristol-Myers Squibb have announced the results of a phase I/II trial of their investigational fully human anti-CTLA-4 antibody MDX-010 for the treatment of melanoma. Study data yielded evidence of efficacy, with 8 of the 36 patients experiencing objective response, including 3 complete responses and 5 partial responses. All three complete responses are ongoing, with 2 through 12 months and 1 through 16 months; partial responses ranged from 7 months to an ongoing response of 19 months. 5 patients experienced serious adverse events, including colitis, uveitis, pancreatitis, arthritis and laryngospasm. This open-label, dose-ranging study enrolled 36 patients with metastatic disease, who were randomized into 1 of 4 3-patient dosing cohorts (0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg and 2.0 mg/kg) or a high dose cohort (3.0 mg/kg; n=24); all patients received MDX-010 treatment once every three weeks, in addition to a high-dose regimen of IL-2.
February 7, 2005
Millennium Pharmaceuticals and Johnson & Johnson Pharmaceutical R&D reported results of a pair of phase II studies investigating the approved drug Velcade (bortezomib) for the treatment of non-Hodgkin’s lymphoma (NHL). The first study found indications of efficacy, with objective remission noted in 7 of 9 patients with follicular lymphoma (1 durable CR, 1 unconfirmed CR, 5 PR), 5 major remissions and 4 stable disease states in the 10 patients with mantle cell lymphoma, and 2 of 2 patients with nodal marginal zone lymphoma responding. Total response rate was 58%. Adverse events were generally manageable and anticipated, including thrombocytopenia, lymphopenia, neuropathy, hypoatremia, hypokalemia, and prothrombin time. The second study yielded similar findings, with 12 of 29 patients with mantle cell lymphoma (6 CR, 6 PR) and 4 of 21 patients with B-cell lymphoma experiencing objective response. Adverse events were also similar and manageable, and included thrombocytopenia, gastrointestinal events, fatigue, neutropenia, peripheral neuropathy, dizziness, and myalgia. Both studies were open-label trials which treated patients with single agent Velcade (1.5 mg/m2) twice weekly for 2 weeks, followed by a week dose free; the first enrolled 24 evaluable patients with NHL (follicular, mantle cell, small lymphocytic and marginal zone) refractory to no more than 3 prior therapies with no limit on total number of treatment cycles; the second study enrolled 40 patients with NHL (mantle cell or B-cell) refractory to any number of prior regimens for a maximum of 6 cycles.
Sanofi-Aventis announced positive preliminary results from a clinical trial of their approved drug Eloxatin (oxaliplatin), for the treatment of colorectal cancer. The trial, dubbed “TREE-2,” assessed the drug as a first-line treatment for the disease in combination with Genentech’s Avastin (bevacizumab). The trial found that the addition of bevacizumab to chemotherapy regimens involving Eloxatin and one of three fluoropyrimidine treatments (FOLFOX, bFOL, or CAPEOX), produced no unexpected toxicities, and preliminary evidence indicated improved efficacy, especially with the FOLFOX and CAPEOX regimens. This randomized, multi-center study enrolled 213 subjects with treatment naïve metastatic colorectal cancer, who received one of the three chemotherapy regimens in combination with bevacizumab. The company announced that they expected to present full results of this trial in May 2005 at the 41st Annual Meeting of the American Society of Clinical Oncology.
January 31, 2005
Genentech issued positive results of a phase IIIb study of Avastin (bevacizumab) in combination with FOLFOX4 chemotherapy, for the second-line treatment of metastatic colorectal cancer. Preliminary results met their primary endpoint, producing a significant reduction in risk of death (hazard ratio=0.74) and a 17% improvement in median survival time (2.5 months vs. 10.7 months), vs. subjects receiving FOLFOX4 alone. The safety and tolerability profile for the combination therapy was consistent with those observed for both drugs alone; the most frequent serious adverse events were bleeding (3/286) and thrombosis (13/286), and the most frequent adverse events were hypertension (17/286) and (44/286) sensory neuropathy. This randomized, controlled, multicenter trial enrolled 829 patients with advanced colorectal cancer refractory to 5-FU-based and irinotecan therapies.
OSI Pharmaceuticals and Genentech reported results of a phase III trial of their approved EGFR inhibitor Tarceva (erlotinib) for the treatment of advanced pancreatic cancer. The study found that adding Tarceva to a standard regimen of gemcitabine chemotherapy significantly improved survival, with 24% of patients receiving the drug combination reaching 1 year survival, vs. 17% for gemcitabine plus placebo (hazard ratio = 0.81, p=0.025), with median survival rates of 6.4 and 5.9 months, respectively. Progression-free survival was significantly improved (hazard ratio=0.76, p=0.003), although significant improvement was noted in tumor response rate (9% vs. 8%, p>0.05). No unexpected safety issues were raised, with no indication of drug-drug interactions between Tarceva and gemcitabine leading to new adverse events. This double-blind, placebo-controlled multi-center study randomized a total of 569 subjects to receive gemcitabine plus either 100 mg/day Tarceva or placebo (n=521), or 150 mg/day Tarceva or placebo (n=48), until disease progression. The study had sites in the United States, Asia, Canada, Europe, Australia and South America, and was headed by the National Cancer Institute of Canada Clinical Trials Group.
Pro-Pharmaceuticals announced preliminary results from a phase I trial of Davanat, their polysaccharide chemotherapy delivery vehicle, for the treatment of solid tumors. Study data indicated that the drug, both alone and in combination 5-FU chemotherapy, met the primary safety endpoints, with no dose limiting toxicity attributable to Davanat observed. Furthermore, preliminary evidence of efficacy with Davanat/5-FU was observed, with 45% of subjects achieving stable disease. This ongoing open-label study has completed enrollment with 40 subjects with advanced solid tumors not amenable to surgery, radiation, or chemotherapy. Subjects received escalating doses of Davanat alone and in combination with 5-FU chemotherapy over 2 28-day treatment cycles.
December 6, 2004
Genentech reported positive results of a phase III study of Avastin (bevacizumab), their monoclonal antibody approved for the treatment of non-small cell lung cancer, for the treatment of colorectal cancer. Interim results indicated that the addition of Avastin to a standard chemotherapy regimen produced a 26% reduction in the risk of death, compared to chemotherapy alone. Furthermore, the drug produced a 17% improvement in median survival time (12.5 vs. 10.7 months). This randomized, controlled, multicenter trial enrolled 829 patients with advanced refractory colorectal cancer, who received a standard FOLFOX4 chemotherapy regimen (oxaliplatin/5-FU/leucovorin) with or without Avastin. Genentech announced that they planned to discuss filing of an sBLA with the FDA based upon these results.
Genmab has announced positive preliminary results from a phase I/II trial of HuMax-EGFr, for the treatment of head and neck cancer. The trial used two neural imaging techniques to examine tumor size and function following 4 weekly doses of the drug. The first technique, which measured disease state by metabolic activity, found that of the 15 subjects evaluable by this method, 6 showed a partial metabolic response (PMR) and 3 patients out of the 15 showed a stable metabolic disease (SMD). All patients showing response were in one of the three highest dose cohorts, and all subjects in the two highest dose cohorts experienced either PMR or SMD. The second imaging technique, which measured tumor size, found that of the 16 patients evaluable by this method, 2 showed a partial response (PR) and 8 showed stable disease (SD). All responses occurring in one of the four highest dose groups, and six out of 7 patients in the two highest groups obtained a PR or SD. This open-label study enrolled a total of 17 subjects, who were randomized to receive a single-treatment of one of six doses of the drug (0.15, 0.5, 1, 2, 4 or 8 mg/kg), followed by a 28 day safety washout and subsequent treatment once weekly for 4 weeks at the same dose. The company announced that they expected additional data from the trial in 2005.
Point Therapeutics has announced positive interim results of a phase II trial of talabostat (PT-100), for the treatment of refractory non-small cell lung cancer (NSCLC). Data from the first 20 subjects met their interim efficacy requirements, with 2 subjects experiencing a reduction in tumor size of 50% or greater. Additional efficacy was observed in the secondary endpoint, with a median time to tumor progression of 24 weeks, compared to a historical baseline of 14. This open-label study plans to enroll a total of 41 patients with unresectable NSCLC, all of whom will receive daily oral talabostat for 2 weeks, following a standard dose of the chemotherapeutic taxotere. Achievement of this interim milestone allows the company to continue enrolling patients up to the full planned cohort size.
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.<
October 4, 2004
Ariad Pharmaceuticals reported interim results of a pair of phase I single-agent study of AP23573, their mTOR inhibitor for the treatment of solid tumors. Trial results showed to drug to be efficacious in treating solid tumors, with 49% (24 of 49) of subjects demonstrating a tumor response; this included 9 partial responses (reduction of tumor size by at least 30%), 5 partial responses (reduction of tumor size by 15%-29%), and 14 disease stabilizations. Median response was 5 months, with some responses extending to 18 months. The drug was well tolerated in both trials, with oral mucositis observed as the dose limiting toxicity. The two trials have to date enrolled a total of 49 subjects with mixed solid tumors; 27 subjects in a daily-dosing investigation and 22 subjects on a weekly-dosing regimen. Both trials are ongoing.
Bayer Pharmaceuticals and Onyx Pharmaceuticals reported the results of a phase II single-agent study of BAY43-9006, their RAF kinase/VEGFR inhibitor being investigated for the treatment of advanced hepatocellular carcinoma (HCC), at the 16th meeting of the American Association for Cancer Research – National Cancer Institute – European Organization for Research and Treatment of Cancer in Geneva, Switzerland. Results of the trial indicated that the drug demonstrated significant efficacy, with 43% of subjects demonstrating 4-month stable disease state, 4% of subjects demonstrating a reduction in tumor size of 25% to 50%,and 5% of subjects demonstrating tumor shrinkage of 50% or more. Median survival rate for all subjects was 9.2 months, and median time to progression was 4.2 months. The open label study enrolled a total of 137 treatment-naïve patients with advanced HCC, all of whom received 400 mg. twice daily in continuous 4-week regimens. Based on this data, the companies announced plans to initiate a phase III single-agent trial, as well as a phase II chemotherapy adjuvant trial.
Epimmune Inc. announced positive combined results of two phase I trials of their multi-epitope cancer vaccine candidate EP-2101, for the treatment of non-small cell lung cancer (NSCLC) and colorectal cancer. Preliminary efficacy data have indicated that the vaccine is strongly immunogenic, with 93% of subjects demonstrating immunological response to at least 1 of the 9 antigenic vaccine components, 53% of subjects demonstrating response to 5 of the 9, and a median response to 4 of the 9. The vaccine was safe and well tolerated. The trials enrolled a total of 24 subjects with stage IIB/IIIA NSCLC or stage III colorectal cancer, all of whom received a total of 6 treatments with the vaccine, once every three weeks for 18 weeks. Following the results of these two investigations, Epimmune announced plans for the initiation of a phase II trial in NSCLC, to be initiated by the end of 2005.
August 25, 2003
Antigenics reported positive results from a phase II trial investigating Oncophage (HSPPC-96), an individualized vaccine for the treatment of colorectal cancer. Results showed that more than half of the subjects who received Oncophage demonstrated a statistically significant immunological response. In addition, subjects who demonstrated an immune response to Oncophage treatment also experienced a significantly lower rate of recurrence (41%) compared with nonresponding subjects (92%). Subjects who responded demonstrated a two-year overall survival rate of 100%, compared with 50% for nonresponders. The study enrolled 29 subjects with stage IV colorectal cancer that had spread to the liver and who had undergone complete resection. Results were published in the August 15, 2003 issue of Clinical Cancer Research.
CEL-SCI reported positive results from a clinical study investigating Multikine, a mixture of human cytokines for the treatment of head and neck cancer. Results demonstrated that two subjects showed complete regression and two subjects showed partial regression of disease. Data also showed tumor fragmentation and the appearance of multinucleated macrophages. No serious adverse effects of treatment were reported. The study enrolled twelve previously untreated subjects with head and neck cancer who were treated by peritumoral injection of Multikine in addition to zinc sulfate, indomethacin and cyclopho-sphamide. Results were reported in Archives of Otolaryngology - Head & Neck Surgery, August 2003; Volume 129: 874-881.
May 26, 2003
Genentech reported positive results from a phase III trial investigating Avastin (bevacizumab) plus chemotherapy for the treatment of metastatic colorectal cancer. Results showed that the study in previously untreated subjects met its primary endpoint of improving overall survival. Data showed the trial also met the secondary endpoints of progression-free survival, response rate, and duration of response. The multi-center, randomized study enrolled more than 900 subjects to receive either Avastin plus the standard of care chemotherapy (5-FU/Leucovorin/CPT-11, called the Saltz regimen) or the Saltz regimen plus placebo. The addition of Avastin to chemotherapy was well tolerated. The company plans to submit data from this trial to the annual meeting of the American Society of Clinical Oncology, May 31 - June 3.
December 16, 2002
Titan Pharmaceuticals reported mixed results from a phase III trial investigating CeaVac, a monoclonal antibody for the treatment of metastatic colorectal cancer. CeaVac failed to demonstrate a statistically significant improvement in the primary endpoint of survival in the overall efficacy, but a trend toward 2-3 month survival improvement was shown in subjects receiving at least 5 doses. The randomized, placebo-controlled study enrolled 631 subjects receiving chemotherapy with 5- flourouracil (5-FU) and leucovorin for metastatic colorectal cancer. Subjects in the study received injections of CeaVac once every two weeks for 2 months and then once per month after. Treatment with CeaVac was generally well tolerated, with the most common side effect being local injection site irritation.
August 5, 2002
Results of a phase II trial of URSO 250 for the prevention of the recurrence of colorectal adenomatous polyps showed no statistically significant differences between the URSO 250 group and the placebo group. 594 subjects who had undergone the removal of a colorectal adenoma or a localized early stage cancerous tumor were given URSO 250 or placebo for a treatment period of one year. At a one-year follow-up, the number, size and histology of colorectal polyps were recorded. In the overall study population, there was no statistically significant difference in mean number of recurring polyps between the URSO 250 and placebo groups. However, says Axcan Pharma, in a sub-group of subjects with early stage colorectal cancer, there was a confirmed trend showing a 26% reduction of polyp recurrence rate in the URSO 250 group.
July 29, 2002
In a phase II study of AVI BioPharma's cancer vaccine Avicine for the treatment of stage IV colorectal cancer, anti-hCG antibodies were identified in 56 of the 77 subjects treated and tested for immune response. In addition, all vaccinated subjects demonstrated a median survival of 34 weeks, and subjects who had higher anti-hCG antibody levels showed a median survival of 45 weeks. Furthermore, subjects who produced the antibodies to two segments of the hCG peptide exhibited a median survival of 66 weeks. The vaccine was well tolerated and did not produce severe toxicities attributed to conventional chemotherapy treatment.
May 28, 2002
Study results demonstrated that two phase III trials of Johnson & Johnson's R115777 in gastrointestinal cancers did not achieve their primary endpoints. The first trial was designed to compare treatment with gemcitabine (GEM) and R115777 to GEM and placebo in subjects with locally advanced or metastatic pancreatic cancer. The primary endpoint of the randomized, double-blind, 688-subject trial was median overall survival. Data showed no statistically significant differences in survival between the two groups (193 days for GEM/115777 versus 182 days for GEM/placebo). The second trial evaluated R115777 in 368 subjects with advanced refractory colorectal cancer who had failed two or more prior chemotherapy regimens. The median overall survival for subjects receiving R115777 was 5.7 months compared to 6.1 months for placebo-treated subjects.
May 6, 2002
Phase II trial results suggest a strong correlation between clinical response and pharmacological action for GD0039, GlycoDesign's lead anti-cancer drug. The trial, which was conducted at five Canadian centers, included 18 subjects with metastatic renal cancer and 22 subjects with metastatic colorectal cancer resistant to 5-fluorouracil. In 14 trial subjects, the cell-surface carbohydrate structures targeted by GD0039 were highly inhibited. Within this population, four of six renal cancer subjects and three of eight colorectal cancer subjects experienced tumor shrinkage or stable disease.
February 19, 2002
Pharmacia reported that they are discontinuing their colorectal cancer clinical trial program for SU5416, a small molecule angiogenesis signaling inhibitor. The decision was based on results from a planned interim analysis of a large phase III study. Data showed that the study would not achieve the defined trial endpoints due to a lack of clinical benefit. The phase III study was designed to evaluate standard chemotherapy treatment with or without SU5416 in patients with advanced stage colorectal cancer. The company will also be working with all other SU5416 study investigators to bring the remaining trials to an appropriate conclusion. The SU5416 program was under development by Sugen, a subsidiary of Pharmacia.
Interim results were reported from 30 subjects in a phase II trial of Aphton's G17DT. The trial is designed to evaluate G17DT in combination with chemotherapy (cisplatin plus 5FU/Leucovorin) in subjects with metastatic gastric cancer. When chemotherapy was administered with G17DT, subjects completed an average of 5.5 cycles of chemotherapy, compared to a normal average of 2.5 cycles prior to discontinuation due to side effects. Results showed an overall response rate of 50% - 14 of the 30 subjects experienced a partial response, and one experienced a complete response.