October 17, 2016
Merrimack Pharmaceuticals reported results
of a phase III study of Onivyde (irinotecan liposome
injection) in combination with fluorouracil
(5-FU) and leucovorin for patients with metastatic
pancreatic ductal adenocarcinoma (mPDAC) following
treatment with gemcitabine-based therapy.
The overall survival advantage of Onivyde
in combination with 5-FU and leucovorin versus
5-FU and leucovorin alone was maintained in this
extended analysis: 6.2 months versus 4.2 months
(p=0.039, hazard ratio (HR) =0.75, 95% CI: [0.057-
0.99]). The probability of survival at one year was
greater in the Onivyde combination arm of the
study when compared to the 5-FU and leucovorin
arm: 12-month overall survival estimates of
26% (95% CI, 18-35%) were observed in the
Onivyde combination treatment arm compared
to 16% (95% CI, 10-24%) for 5-FU and leucovorin
arm. The overall response rate (ORR) for the
Onivyde plus 5-FU and leucovorin arm was 16%
versus 1% for the 5-FU and leucovorin arm
(p<0.0001). Treatment with Onivyde in combination
with 5-FU and leucovorin provided a
two-fold improvement in disease control rate
compared with 5-FU and leucovorin alone (52%
v. 24%, respectively). Final results suggest that
patients treated with Onivyde in combination
with 5-FU and leucovorin had no notable deterioration
in quality of life at 12 weeks despite the
addition of a second chemotherapeutic agent
to 5-FU and leucovorin. No new safety concerns
were noted and the overall safety profile was
manageable with the most common grade three
adverse events of neutropenia, diarrhea, fatigue,
vomiting and asthenia.
January 25, 2016
Merrimack Pharmaceuticals issued results of a phase III study of ONIVYDE (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin achieved a substantial improvement in 12-month overall survival in patients with post-gemcitabine metastatic pancreatic adenocarcinoma when compared to 5-FU and leucovorin alone. The randomized, open label study in patients with metastatic adenocarcinoma of the pancreas who received prior gemcitabine-based therapy was the largest phase III study in this setting to date. A total of 417 patients were randomized across the three arms. Primary survival analysis was based on 313 events and showed that ONIVYDE in combination with 5-FU and leucovorin significantly improved overall survival v. 5-FU and leucovorin alone: 6.1 months v. 4.2 months (p=0.012, unstratified hazard ratio (HR) =0.67, 95% CI: [0.49-0.92]). The monotherapy regimen in this study did not show improvement over the 5-FU and leucovorin arm: 4.9 v. 4.2 months (p=0.94, HR=0.99, 95% CI: [0.77-1.28]). No new safety or tolerability concerns were note in the updated analysis. The primary NAPOLI-1 study results were the basis of the recent FDA and Taiwan FDA approval of ONIVYDE in combination with 5-FU and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. Merrimack and Baxalta have entered into an exclusive licensing agreement for the development and commercialization of ONIVYDE outside of the U.S. and Taiwan. Baxalta’s marketing authorization application for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy is currently under review with the EMA.
Novocure issued results of a phase II trial showing Tumor Treating Fields (TTFields) therapy plus first-line chemotherapy gemcitabine is tolerable and safe in patients with advanced pancreatic cancer. The first cohort of the prospective, single-arm study included 20 patients with advanced pancreatic cancer whose tumors could not be removed surgically and who had not received chemotherapy or radiation therapy prior to the clinical trial. The primary endpoint measured the incidence and severity of treatment-related adverse events. As a result of TTFields therapy, 10 patients experienced treatable contact dermatitis. No serious adverse events related to TTFields were reported. Fourteen patients reported serious adverse events unrelated to TTFields therapy. In relation to these reported results for gemcitabine alone, PANOVA patients who received TTFields therapy plus first-line gemcitabine experienced a median progression free survival of 8.3 months compared to 3.7 months, a median overall survival of 14.9 months compared to 6.7 months and a median one-year survival of 55% compared to 22%. Thirty percent of the evaluable tumors had partial responses compared to 7% with gemcitabine alone and another 30% had stable disease. The PANOVA trial includes a second cohort testing TTFields plus gemcitabine and nab-paclitaxel in an additional 20 patients. Based on these data, the company will accelerate planning of a phase III clinical trial in pancreatic cancer.
January 26, 2015
PharmaEngine released results of a
phase III study of MM-398 (PEP02, liposome
irinotecan injection) for metastatic pancreatic
cancer. The global, randomized, openlabel
study evaluated two MM-398 regimens,
80mg/m2 combined with 5-fluorouracil (5-
FU) and leucovorin (LV) every two weeks, and
120mg/m2 as a monotherapy every three
weeks. Each arm was compared to a control
arm of 5-FU and LV. A total of 417 patients
were randomized across the three arms. Each
MM-398 regimen was compared against the
control arm on the primary endpoint of overall
survival. Patients were enrolled at 76 sites
of the 105 sites initiated in North America,
South America, Europe, Asia and Australia.
The primary analysis demonstrated a statistically
significant increase in overall survival
with an unstratified hazard ratio of 0.67 (95%
CI [0.49-0.92], p=0.0122) and a median of
6.1 months for the combination of MM-398
plus 5-FU/LV compared to 4.2 months in the
5-FU/LV control arm. In the stratified analysis,
which accounts for pre-specified prognostic
factors included in the study randomization
stratification, the overall survival for MM-398
in combination with 5-FU/LV compared to
control arm resulted in a hazard ratio of 0.57
(95% CI [0.41-0.80], p=0.0009). In the Per
Protocol population (defined by patients
who received 80% of protocol defined dose
and were able to remain on treatment for
at least six weeks), MM-398 in combination
with 5-FU/LV demonstrated superior overall
survival and tumor control to the control arm
of 5-FU/LV alone. In the Per Protocol analysis,
median overall survival for the combination
therapy arm was 8.9 months versus 5.1
months in the control arm (stratified HR =
0.47, 95% CI [0.29-0.77], p=0.0018).
September 9, 2013
Incyte issued results of a phase II trial of ruxolitinib, its oral JAK1 and JAK2 inhibitor, in combination with capecitabine in patients with recurrent or treatment refractory metastatic pancreatic cancer. The randomized, double-blind, placebo-controlled trial enrolled 136 patients. The hazard ratio (HR) for overall survival (OS) in the intent to treat population was 0.79 (one-sided p=0.12), and in a pre-specified subgroup analysis conducted in patients identified prospectively as most likely to benefit from JAK pathway inhibition, the HR for OS was 0.47 (one-sided p=0.005). Within this subgroup of patients, which represented 50% of the randomized population, six-month survival in the ruxolitinib arm was 42% v. 11% for placebo. Durable tumor responses were observed only in patients receiving ruxolitinib, and ruxolitinib-treated patients achieved a significant improvement in body weight relative to placebo. A phase III trial will be reviewed with the FDA.
August 12, 2013
Immunomedics reported results of a phase Ib study of 90Y-labeled-clivatuzumab for the treatment of metastatic pancreatic cancer in 58 patients who had received at least two prior treatments. Patients were randomized to receive either 90Y-labeled-clivatuzumab once a week for three weeks at 6.5mCi/m2 with gemcitabine 200mg/m2 given weekly for four weeks (Arm A) or 90Y-labeled-clivatuzumab alone (Arm B). This treatment cycle was repeated every four weeks until unacceptable toxicity, patient deterioration or patient withdrawal. Patients were followed for one year or until death. The median overall survival (OS) for Arm A (N=27) was 119 days, an improvement over Arm B (N=26), with a median OS of 80 days (P=0.04). For the 23 patients who received multiple cycles of therapy, the median OS increased to 157 days in Arm A compared with 103 days in Arm B. Survival also was related to patients’ Karnofsky Performance Status (KPS) scores at study entry, increasing from a median of 79 days for patients with 80% KPS to 119 days for patients with 90% to 100% KPS. In contrast, increased number of prior treatments is a negative prognostic indicator for survival. The median OS decreased from 90 to 82 to 73 days for patients who received 2, 3 or 4 to 5 prior treatments, respectively. Phase III trials are planned for 2013 or the beginning of 2014 in the U.S. and the E.U.
June 17, 2013
Halozyme Therapeutics reported results from a phase Ib trial of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) for the treatment of stage IV metastatic pancreatic cancer. The single-arm phase Ib trial enrolled 28 stage IV treatment naïve pancreatic ductal adenocarcinoma patients. The overall response rate (complete response + partial response) by RECIST 1.1 criteria was 42% (95% CI 22-62) for those treated at therapeutic dose levels of PEGPH20 (1.6 and 3.0μg/kg) as assessed by an independent radiology review (n=24). Additionally, in subjects with high levels of hyaluronan (HA), a substance found in a protective matrix that surrounds many pancreatic cancers, the overall response rate was 64% (seven of 11 subjects with available biopsy). Moreover, 43% (six of 14 subjects) saw a reduction of at least 70% in serum carbohydrate antigen 19-9 (CA 19-9), a biomarker that often correlates with tumor cell burden. Treatment was generally well tolerated, and the adverse event profile was consistent with those seen in previous studies of PEGPH20 as a single agent and as previously reported for gemcitabine alone. The most common adverse events were muscle spasms, myalgia and arthralgia (all grade 1/2). There was no evidence of new toxicities when used in combination with gemcitabine. The results support the dosing regimen at 3μg/kg, being used in the phase II trial.
February 18, 2013
Peregrine Pharmaceuticals released results from a phase II trial of bavituximab in combination with gemcitabine Stage IV pancreatic cancer. This open-label, randomized study enrolled 70 patients with previously untreated, advanced Stage IV pancreatic cancer. Subjects received either bavituximab in combination with gemcitabine, or gemcitabine alone. Data demonstrated the combination of bavituximab and gemcitabine resulted in more than a doubling of overall response rates (ORR) and an improvement in overall survival (OS) when compared with gemcitabine. Subjects treated with a combination of bavituximab and gemcitabine had a 28% tumor response rate as compared to 13% in the control arm. Median OS, the primary endpoint of the trial, was 5.6 months for the bavituximab plus gemcitabine arm and 5.2 months for the control arm (HR=0.75). Bavituximab was generally safe and well tolerated, with similar adverse events occurring in both arms. Peregrine is evaluating the next steps for advancing the bavituximab pancreatic program to include combination with other cancer agents. Bavituximab is currently being evaluated in patients with non-small cell lung, breast, prostate, liver and rectal cancers in combination with approved chemotherapies and radiation.
February 11, 2013
Seattle Genetics released interim results for a phase I trial of ASG-5ME for the treatment of metastatic pancreatic ductal adenocarcinoma (PDA). This dose-ranging, placebo-controlled study enrolled 35 patients with metastatic PDA who were heavily pre-treated with a median of three prior therapies. Subjects received doses of ASG-5ME ranging from 0.3mg/kg to 1.5mg/kg weekly for three out of every four weeks, or placebo. Results showed that ASG-5ME 1.2mg/kg was the maximum tolerated dose. Of the patients receiving ASG-5ME 1.2mg/kg, one patient achieved a partial response, six patients achieved a stable disease and four patients had progressive disease. Seven patients were not evaluable for response. The drug was well tolerated. The most frequent adverse events were fatigue, vomiting, decreased appetite, abdominal pain and nausea. Based on these data, Seattle Genetics will continue the phase I trial.
January 28, 2013
Celgene International issued results from a phase III trial of Abraxane in combination with gemcitabine for the treatment of metastatic pancreatic cancer. This open-label, randomized, international study, MPACT, enrolled 861 treatment-naïve patients with metastatic pancreatic cancer. Subjects received 125mg/m2 Abraxane plus 1000mg/m2 gemcitabine for three weeks, followed by a week of rest, or 1000mg/m2 gemcitabine alone for seven weeks, followed by a week of rest. Data demonstrated a statistically significant improvement in overall survival in the Abraxane/gemcitabine arm compared to patients receiving gemcitabine alone (median of 8.5 vs. 6.7 months) (HR 0.72, p=0.000015). Results showed the Abraxane/gemcitabine arm demonstrated a 59% increase in one-year survival (35% versus 22%, p=0.0002) and demonstrated double the rate of survival at two years (9% versus 4%, p=0.02) as compared to gemcitabine alone. Furthermore, the Abraxane/gemcitabine arm demonstrated a 31% reduction in the risk of progression or death with a median progression-free survival of 5.5 versus 3.7 months (HR 0.69, P=0.000024) and an overall response rate of 23% compared to 7%. The drug was well tolerated. The most frequent adverse events were neutropenia, fatigue and neuropathy. Based on these results, Celgene International plans to submit dossiers for registration in the U.S. and Europe during the first half of 2013, followed by submissions in other countries/regions during the second half of 2013.
June 11, 2012
Antisense Pharma reported results from a phase I/II trial of trabedersen for the treatment of advanced pancreatic cancer. This open-label, multi-center, dose-escalation study enrolled 61 patients with KPS ≥ 80%. Subjects received continuous intravenous trabedersen as second- and fourth-line therapy in escalating doses in one of two treatment schedules for up to 10 cycles: one week on followed by one week off; four days on followed by 10 days off. The second schedule was determined to be most successful, and applied to all subjects in the phase II part of the study. Subjects with advanced pancreatic cancer revealed a mOS of 4.9 months (n≡37; 95% CI: 3.2, 7.1) and a mOS of 13.4 months (n≡9; 95% Cl: 4.9, 18.2). Dose-limiting toxicities, seen in one or two subjects each, were maculopapular rash, reversible thrombocytopenia and gastrointestinal hemorrhage. Antisense did not note their plans for trabedersen.
March 5, 2012
BioSante issued results from a phase Ib trial of GVAX Pancreas cancer vaccine. This trial enrolled 30 subjects with previously treated, locally advanced or metastatic pancreatic adenocarcinoma who received GVAX plus ipilimumab (Yervoy) or ipilimumab alone. The addition of GVAX Pancreas cancer vaccine to ipilimumab increased the median survival from 3.3 months for the monotherapy to 5.5 months for the combination therapy, an increase of over 60%. The combination also demonstrated an increase in one year survival, from 7% to 27%.
February 27, 2012
Threshold Pharmaceuticals released results from a phase IIb trial of TH-302 for the first line treatment of pancreatic cancer. The open label trial, TH-CR-404, enrolled approximately 200 subjects with first line advanced pancreatic cancer. The subjects received TH-302 at a dose of 240 mg/m2 or 340 mg/m2 in combination with gemcitabine (1,000 mg/m2) or gemcitabine alone. The primary endpoint was progression free survival (PFS). The combination of TH-302 plus gemcitabine resulted in a 63% improvement in PFS. The median PFS was 5.6 months for subjects treated with gemcitabine in combination with both TH-302 doses compared to 3.6 months for subjects treated with gemcitabine alone p≡0.005). The response rate in the combination arms was 22% compared to 12% in the gemcitabine alone group. Results also demonstrated greater efficacy in the higher TH-302 dose group compared to the lower dose group. The combination was well tolerated and the most frequent adverse events were skin and mucosal toxicities.
February 21, 2011
Oncolytics Biotech released preliminary results from a phase II trial of intravenous Reolysin plus gemcitabine (Gemzar) for the treatment of pancreatic cancer. This single arm, open-label trial, (REO 017) planned to enroll 33 treatment nave subjects with advanced or metastatic pancreatic cancer. The subjects received intravenous Reolysin with gemcitabine every three weeks. The primary objective was to determine the clinical benefit rate (complete response (CR) + partial response (PR) + stable disease (SD). Preliminary data are from six evaluable subjects, all of whom showed symptomatic improvement. Three of six subjects showed SD for 12 weeks or greater.
January 31, 2011
FibroGen released interim results from an ongoing phase I/II trial of FG-3019 for the treatment of pancreatic cancer. This open-label, single-arm, dose-escalation study was enrolling subjects with unresectable pancreatic cancer who received FG-3019 administered every 2 weeks; gemcitabine and erlotinib therapy was added at day 15. Enrollment in the first four dose cohorts (3, 10, 15, and 25 mg/kg FG-3019) was complete at this time. Data are from the first three dose cohorts (n≡17). For the dose cohorts combined, the median overall survival was 9.1 months and median time to progression was 4.7 months, with longest overall survival (median 9.4 months) and time to progression (median 7.7 months) observed in the highest dose cohort (15 mg/kg). Best response according to RECIST showed one partial response, nine subjects had stable disease, two progressed, and three were not evaluable. In addition, reduced metabolic activity in the primary tumor was observed in all five subjects who received the highest dose of FG-3019 prior to initiating chemotherapy; three of these five showed a partial metabolic response. Survival was significantly higher for subjects with low plasma levels of connective tissue growth factor at baseline.
New Link Genetics reported results from a phase II trial of their immunotherapy for pancreatic cancer, HyperAcute-Pancreas. This open label, single arm trial, NGL0205, treated 70 subjects with stage I or II pancreatic caner undergoing surgical resection. The subjects received HyperAcute-Pancreas with standard adjuvant therapy (gemcitabine + 5-FU-XRT) for mean of 12 doses. Disease free survival and overall survival are the primary and secondary endpoints, respectively. The current median disease free survival is 16 months, an improvement over 11 months based on historical data. The estimated survival rates at 12 and 24 months are 91% and 54%, respectively, compared to the expected rates of 63% and 32% based on historical data. The overall survival data continues to mature. HyperAcute-Pancreas was well tolerated. The most common adverse events were injection site pain and induration
November 8, 2010
BioCancell released positive results from a phase I/II trial of BC-819 for the treatment of pancreatic cancer. The trial enrolled nine subjects with unresectable, locally advanced pancreatic cancer at one site in the U.S. and one site in Israel. The subjects each received four doses of BC-819 (4 mg or 8 mg), twice per week for two weeks. The primary endpoint, drug safety, was achieved with no side effects definitely connected to BC-819. A secondary endpoint was preliminary efficacy of the treatment on the local pancreatic tumor alone. Results show that within a month from commencement, the local tumor had not increased in size in eight out of the nine subjects, and of those examined three months after commencement, three out of five (60%) of the subjects in the higher-dose cohort showed significant shrinkage of the tumor and no appearance of metastases based on RECIST criteria. Two additional subjects met the criteria for stable disease (no significant change in the size of the pancreatic tumor and no appearance of metastases after three months). In total, 5 out of 8 subjects (62.5%) tested after three months showed significant tumor reduction or stability, along with prevention of metastases.
July 12, 2010
Novartis issued positive results from a phase III trial of everolimus for the treatment of pancreatic neuroendocrine tumors. This U.S-based, double-blind, randomized, parallel group, placebo-controlled trial, RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors), enrolled 410 subjects. The subjects received everolimus (10 mg/day) plus best supportive care or placebo plus best supportive care. The primary endpoint, progression free survival, was reached. Everolimus extended median progression-free survival from 4.6 to 11.0 months versus placebo and reduced risk of cancer progression by 65% (p<0.0001). There were no unexpected adverse events.
June 7, 2010
Novartis issued positive preliminary results from a phase III trial of everolimus for the treatment of pancreatic neuroendocrine tumors. This U.S-based, double-blind, randomized, parallel group, placebo-controlled, dubbed RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors) enrolled 410 subjects with advanced pancreatic neuroendocrine tumors. The subjects received everolimus (10 mg/day) pplus best supportive care or placebo plus best supportive care. The primary endpoint, progression free survival, was reached. The addition of everolimus to best supportive care significantly extended progression-free survival compared to best supportive care alone.
April 26, 2010
Abraxis reported positive results from a phase I/II trial of Abraxane plus gemcitabine for the treatment of pancreatic cancer. This open label study enrolled a total of 67 subjects. In the phase I portion, the subjects received weekly doses of Abraxane (100, 125, or 150 mg/m2) in combination with gemcitabine (1,000 mg/m2) for three weeks (on days one, eight and 15) with one week of rest. The primary safety endpoint was the identification of the maximum tolerated dose and dose-limiting toxicities. The recommended dose for the phase II portion was determined to be 125 mg/m2 Abraxane plus 1000 mg/m2 gemcitabine. In the 44 subjects treated at this dose, the median overall survival time was 12.2 months, doubling the historical control of gemcitabine administered alone. The combination also resulted in a confirmed overall response rate in 50% of the subjects and a disease control rate of 68%. In the overall study (n=67), three patients achieved a complete response.
June 29, 2009
Pfizer reported positive results from a phase III trial of sunitinib for the treatment of pancreatic neuroendocrine tumors. This trial enrolled 154 subjects with progressive, well-differentiated, malignant pancreatic islet cell tumors who had progressed in the last 12 months. The subjects were randomized to either the sunitinib (37.5 mg/day, continuous daily dosing) plus best supportive care or placebo plus best supportive care. The primary endpoint, progression free survival was reached; the median progression-free survival was 11.1 months in the sunitinib arm compared to 5.5 months in the placebo arm (p< 0.001). Sunitinib was well tolerated in this population.
September 22, 2008
Novartis reported positive results from a phase II trial of RAD001 for the treatment of pancreatic neuroendocrine tumors. This international, multi-center, open label, stratified study, dubbed RADIANT-1 (RAD001 In Advanced Neuroendocrine Tumors), enrolled 160 subjects who became resistant to prior treatment with cytotoxic chemotherapy. The subjects received either daily RAD001 combined with monthly Sandostatin LAR Depot (standard of care) or daily RAD001 alone. The primary endpoint was objective response rate (complete response and partial response). In the RAD001 monotherapy group, overall response rate plus stable disease rate was seen in 77% of the population. The overall response rate for patients who received RAD001 alone was 8%; all responses were partial. In addition, 69% of subjects experienced stable disease and 14% experienced progressive disease. Responses were maintained for a median of 10.6 months and the median progression free survival was 9.3 months. Median overall survival had not been reached at this time. In the combination arm, overall response rate plus stable disease rate was seen in 82% of the population. The overall response rate was 4% and all confirmed responses were partial responses. Stable disease was reported in 78% of the subjects and 2% experienced progressive disease. The median progression free survival was 12.9 months and median overall survival had not been reached. Two phase III trials are currently underway.
May 19, 2008
Pharmexa released negative results from a phase III trial of GV1001 for the treatment of pancreatic cancer. This international, randomized trial, dubbed PrimoVax, enrolled 360 subjects with non-resectable pancreatic cancer. The subjects received standard treatment with gemcitabine chemotherapy or GV1001. If the condition of the subjects receiving GV1001 deteriorated, treatment with gemcitabine was added. The primary endpoint was survival. The preliminary data, based on deaths of 174 subjects, showed that survival was no better in the GV1001 group in which gemcitabine chemotherapy was added when compared to the group that received standard gemcitabine chemotherapy immediately. Based on the results Pharmexa stopped enrollment in this study. A separate phase III study evaluating GV1001 administered during or after chemotherapy is currently underway.
April 14, 2008
MediGene reported positive results from a phase II trial of EndoTAG-1 for the treatment of pancreatic cancer. This randomized, eighteen-month trial enrolled two hundred subjects with inoperable, advanced and metastasized pancreatic cancer, in Europe. The subjects received one of three doses of EndoTAG-1 (11, 22, and 44 mg/m) twice a week for seven weeks, in addition to gemcitabine once a week. In the control group, the subjects received gemcitabine monotherapy once a week. The trial was designed to assess the effect of the drug combination on the six-month survival rate, the tumor response rate, and quality of life. The combination therapy with gemcitabine and EndoTAG-1 resulted in a dose-dependent increase in the median survival time to 8.1 months, 8.8 months, and 9.4 months, respectively in the three EndoTAG-1 groups. The median survival time of the subjects treated with only gemcitabine was 7.2 months. The six-month survival rate also increased dose-dependently, from 63.3 % in the group treated with only gemcitabine, to 66.1 %, 72.4 %, and 80.7 %, respectively in the three EndoTAG-1 groups. A second group of subjects had the opportunity to receive treatment with EndoTAG-1 repeatedly and over a longer period of time. Dependent on the dosage administered, these subjects showed a median survival time of up to 11.5 months. Additional phase II trials of EndoTAG-1 are currently underway.
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.
pSivida issued positive results from a phase IIa trial of Brachysil for the treatment of pancreatic cancer. This trial enrolled seventeen subjects with advanced inoperable pancreatic cancer. The subjects received BrachySil, injected directly into the primary tumors via endoscopic ultrasound, in combination with standard chemotherapy (gemcitabine). CT assessments of response were performed at weeks eight, sixteen and twenty four. The combination treatment was well tolerated, with no significant adverse events related to BrachySil. Data showed disease control in 82% of subjects and an overall median survival of three hundred and nine days. In addition, BrachySil was found to be easily deliverable by endoscopic ultrasound. Based on the results, pSivida plans to commence a phase II dose ranging study in the first quarter of 2008.
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.
August 20, 2007
Cytopia reported positive preliminary results from a phase I trial of CYT997 for the treatment of cancer. This safety and efficacy trial enrolled subjects with a variety of solid tumors who had failed previous therapy or for whom no other therapy exists. The subjects received CYT997 administered as a 24-hour intravenous infusion on a three-weekly cycle, for a maximum of six cycles The primary endpoints, determination of the maximum tolerated dose (MTD) and dose limiting toxicities, were both achieved. The MTD was established at 358 mg/m2 and two reversible dose limiting toxicities were observed; a prolongation of the QTc interval and hypoxia/dyspnoea. Based on the results, Cytopia is planning to initiate phase II trials by the end of 2007.
pSivida released positive preliminary results from a phase IIa trial of BrachySil for the treatment of inoperable pancreatic cancer. This trial enrolled 17 subjects in the United Kingdom and Singapore. Subjects received BrachySil directly to a tumor in the pancreas via endoscopic ultrasound, in combination with standard chemotherapy. The primary endpoint was safety. Secondary endpoints included efficacy (reduction of tumor size) and overall survival. Eight weeks follow-up data shows treatment was well tolerated, with no reports of drug related adverse events. Efficacy data from the first 10 treated subjects shows 90% of these subjects have had either stabilization or reduction in the size of their primary tumor. Full results are expected by the end of 2007.
April 16, 2007
ImClone and Bristol-Myers Squibb announced negative preliminary results from a phase III trial ofErbitux plus gemcitabine for the treatment of pancreatic cancer. This open-label, randomized trial enrolled 700 subjects in the United States and Canada who received Erbitux plus gemcitabine or gemcitabine alone. Results revealed that the primary study endpoint of statistically improving overall survival was not met. The companies plan to fully analyze the data in order to determine the future development of Erbitux for the treatment of pancreatic cancer.
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.
February 5, 2007
Cell Genesys announced positive long-term data from a phase II trial of GVAX for the treatment of operable pancreatic cancer. This trial enrolled 60 subjects who received GVAX after surgical resection of their tumor and adjuvant radiation and chemotherapy. GVAX was administered intradermally before and after standard post-operative adjuvant radiation therapy and 5-flourouracil chemotherapy. Treatment was administered at up to five doses, the first prior to adjuvant chemoradiotherapy, the next three following adjuvant therapy at approximately one-month intervals and the fifth as a booster injection six months later. Treatment was well tolerated through the study duration. The long-term survival results revealed a median survival of 26.8 months. GVAX is currently in phase III trials for the treatment of pancreatic cancer.
Sunesis reported interim results from two phase II trials of SNS-595 for the treatment of small cell lung cancer and non-small cell lung cancer. Both trials employed a two-stage design with an interim assessment between each stage. Objective response rate, as defined by RECIST (Response Evaluation Criteria in Solid Tumors) was the determination for advancing to stage two. All subjects received SNS-595 at the MTD of 48 mg/m2 every three weeks. The small cell cancer trial included a treatment-sensitive arm and a treatment-refractory arm. Nine out of eleven evaluable subjects in the treatment-sensitive arm had stable disease or objective response by the end of two cycles of treatment, which exceeded the pre-specified requirements for advancing to stage two. In the treatment-refractory arm, none of the 20 evaluable subjects reached objective response, although there were reports of stable disease. Based on the data, enrollment in this arm was discontinued. The non-small cell cancer trial enrolled 25 subjects who had previously failed first-line treatment. Although 50% had achieved stable disease or better, objective response rates were not observed. Based on these results, enrollment was discontinued in this trial. Sunesis plans to explore additional clinical evaluation of SNS-595 in combination with other anti-cancer agents in the treatment of non-small cell lung cancer pending the full evaluation of these results.
YM BioSciences released negative results from a phase III trial of tesmilifene combined with epirubicin/cyclophosphamide for the treatment of breast cancer. This trial, conducted under a Special Protocol Assessment by the FDA, enrolled 723 women with metastatic or recurrent breast cancer. Subjects received tesmilifene combined with epirubicin/cyclophosphamide or epirubicin/cyclophosphamide alone. A planned interim analysis was conducted to determine if there was a significant difference in overall survival rates between the two treatment groups, the primary endpoint. Review of the data found that such differences had not occurred and were unlikely to occur during the course of the trial. Based on this information, YM BioSciences terminated this trial.
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.
August 28, 2006
Avantogen released positive preliminary results from a phase I trial of RP101, in combination with gemcitabine chemotherapy, for the treatment of advanced pancreatic cancer. This open label, dose ranging study enrolled 22 subjects who received intravenous doses of Gemcitabine administered at 1000mg/m2 on days 1, 8 and 15 every 28 days and RP101, administered for four consecutive days starting on the day of each gemcitabine administration. Five dose levels of RP101 were evaluated (500, 625, 750, 875 or 1000mg/day). Safety profiles were positive with the most commonly reported adverse events being neutropenia, nausea, vomiting, loss of appetite, fatigue and fever. Pharmacokinetic data revealed a maximum tolerated dose of 750mg/day. Efficacy data revealed positive results with a 6-month survival rate of 68% and a 12-month survival rate of 39%. The median survival was 9.3 months compared to a median survival of 6 months for subjects taking gemcitabine monotherapy and gemcitabine in combination with erlotinib or oxaliplatin. Avantogen planned to submit an IND by Q4, 2006 and initiate phase II trials by early 2007.
May 1, 2006
NeoPharm announced positive results of a phase I trial of cintredekin besudotox (IL13-PE38QQR), for the treatment of malignant glioma, at the 74th Annual Meeting of the American Association of Neurological Surgeons in San Francisco. This open-label study enrolled 19 patients with treatment-naïve malignant glioma, who received single 96-hour infusions of the drug (0.25 mcg/ml or 0.5 mcg/ml) via intraparenchymal catheter, followed by standard fractionated radiation therapy (5940-6100 cGy, 5 days per week for 6-7 weeks) with or without temozolomide (75 mg/m2 per day during radiation). Trial data yielded a positive safety profile for the drug: no dose limiting toxicities (DLT) were observed with either combination using the lower dose; 1 DLT was observed at the higher dose in combination with radiotherapy alone, but 5 additional subjects had received cintredekin plus radiotherapy and 3 had received cintredekin plus radiotherapy & temozolomide without incidence of DLT.
SuperGen has reported negative interim results of a phase II trial of Orathecin for the treatment of first-line pancreatic cancer. The trial had enrolled 39 subjects, who received 1000 mg/m2 gemcitabine every week for three out of four weeks with concurrent 1.5 mg/m2 Orathecin daily for five of seven days each week; treatment cycles were repeated every four weeks until evidence of disease progression was noted or patient withdrawal. Trial data failed to meet the pre-specified threshold for median survival, with median duration of 6.0 months and a 1 year survival rate of 27%. These results were insufficient to warrant phase III studies of the drug under the current development program; SuperGen announced plans to review the Orathecin development effort.
February 6, 2006
Lorus Therapeutics announced positive results of a phase III trial of Virulizin for the treatment of pancreatic cancer, at the 17th International Congress on Anti-Cancer Treatment in Paris. This randomized, double-blind, multicenter study enrolled chemonaive patients with locally advanced or metastatic pancreatic cancer, who received the drug or placebo in addition to a standard regimen of gemcitabine; on disease progression, subjects were permitted to switch to a second line regimen of Virulizin or placebo plus 5-FU or Virulizin or placebo alone. Analysis of study data indicated that, while the first line regimen did not significantly extend survival over gemcitabine alone, subjects with Stage 3 disease who continued to receive Virulizin in a second line regimen experienced significantly improved overall survival (10.9 months), vs. both intent-to-treat (7.4 months; p=0.0178) and efficacy-evaluable (7.4 months; p=0.01890) patients on placebo.
October 24, 2005
Lorus Therapeutics issued negative results of a phase III trial of Virulizin for the first-line treatment of pancreatic cancer. Trial data failed to meet their primary efficacy endpoint, with subjects receiving the drug plus gemcitabine yielding median overall survival of 6.8 months and a 27.2% overall survival rate, compared to 6.0 months and 16.8% for placebo plus gemcitabine ( p>0.05). An exploratory trends towards efficacy was noted in median overall survival the ECOG 0/1 subpopulation (8.0 months vs. 6.3 months; p=0.063). This placebo-controlled study enrolled chemo-naïve pancreatic cancer patients, who received Virulizin or placebo in addition to a standard regimen of gemcitabine. The company announced places to investigate the utility of the drug in subpopulations yielding potential efficacy.
August 8, 2005
Oxford BioMedica reported positive results of the first stage of a phase II trial of their gene targeted prodrug activation product MetXia, for the treatment of pancreatic cancer. Data from this first portion of the trial indicated that the drug was generally safe and well tolerated, and successfully elicited dose- dependent cytochrome P450 gene expression in targeted tumor cells, yielding potential efficacy in facilitating localized cyclosphosphamide chemotherapy following MetXia administration (cyclosphosphamide is metabolized to its active form by cytochrome P450, found normally in the liver). The first stage of the trial enrolled 6 patients undergoing palliative tumor resection for pancreatic cancer at the Royal Liverpool University Hospital in the UK. Subjects received one of 2 dose levels of the drug once before and once after surgery, followed by cyclosphosphamide administration. The company announced that accrual of 25 patients into the second stage of the trial has been initiated; this stage was designed to investigate the efficacy of the drug in improving the therapeutic profile of cyclosphosphamide.
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.
February 14, 2005
Bioaccelerate Holdings and Australian Cancer Technology announced positive results from a phase I/II trial of RP101 (bromovinyl deoxyuridine), for the prevention of chemotherapy resistance in pancreatic cancer patients. The addition of RP101 to gemcitabine-plus-cisplatin chemotherapy produced a significant increase in median survival time from historical baseline for gemcitabine-plus-cisplatin alone (15 vs. 7.5 months, p=0.008), with 76.9% of subjects reaching one year survival. Time to tumor progression was also extended, from 4.75 months to 7.5 months. This extended open-label study enrolled a total of 13 patients with metastatic pancreatic cancer at in Germany. All subjects received 125mg of RP101 four times daily for the first five days of standard chemotherapy with gemcitabine-plus-cisplatin.
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.
September 27, 2004
Maxim Pharmaceuticals has issued negative results of a phase III trial of their investigational immunosupportive drug Ceplene, for the treatment of malignant melanoma. The trial failed to meet its primary endpoint, with no significant increase in patient survival among subjects receiving Ceplene plus Interleukin-2 (IL-2), versus subjects receiving IL-2 alone. This trial was conducted as an extension of a previous trial, which found a significant improvement in patient survival at one, two and three years among a subgroup of its trial population, advanced malignant melanoma patients with liver metastases; results among the entire trial population of this earlier trial were non-significant. This multicenter, randomized, approved-therapy controlled study enrolled 235 subjects across 35 sites in North America and Europe, all of whom had advanced malignant melanoma with liver metastases. Maxim announced that they intended to continue the development of Ceplene for other cancer indications, and announced that data analysis for this trial was ongoing.
OSI, Genentech, and Roche have announced the results of a phase III trial of Tarceva, their HER1/EGFR tyrosine kinase inhibitor, for the treatment of pancreatic cancer. Data demonstrated that a combination of Tarceva plus gemcitabine chemotherapy improved outcomes versus gemcitabine plus placebo, with a significant improvement in overall survival of 23.5%. In addition, Tarceva-plus-gemcitabine produced significant improvements in risk of death, median survival time, percentage of subjects reaching one year survival, and progression free survival time. No significant difference was observed in tumor response. This randomized, double-blind, placebo-controlled study enrolled a total of 569 subjects with advanced metastatic pancreatic cancer at investigative sites worldwide; all subjects received a standard regimen of gemcitabine chemotherapy, plus one of two doses of Tarceva daily or placebo. The companies announced that following final review and publication of trial data, they would be presented to the FDA to determine the next steps for Tarceva’s development in this indication. An NDA for Tarceva is currently under review by the FDA, for second-line monotherapy treatment of advanced non-small cell lung cancer.
Pharmacyclics announced interim results of their phase I trial of Xcytrin for the treatment of non-Hodgkin’s lymphoma. Data from the ongoing study indicate that the addition of Xcytrin to standard therapy (Rituxan-plus-Zevalin) produced no additional safety concerns or adverse effects in any subjects to date. Furthermore, all three subjects treated to date demonstrated complete remission within one month of treatment initiation; one patient experienced remission for nine months, before a localized relapse, and two have experienced continuing remission for two months. Subjects received a single injection of Rituxan and four daily injections of Xcytrin, followed by a second injection of Rituxan coupled with an injection of Zevalin and four more daily treatments with Xcytrin one week later. This open label study plans to enroll a total of 20 treatment-refractory subjects; all three subjects treated to date had failed three previous treatment courses, including Rituxan monotherapy. Pharmacyclics announced their support of ongoing phase I and II trials in a range on cancers.
August 23, 2004
Cell Genesys has reported additional positive results from their phase I study of their GVAX modified-whole-cell pancreatic cancer vaccine. A previously reported phase I trial administered the vaccine to 14 subjects, of which 3 remain alive and disease free as of the most recent 6.5 year follow-up. The new data on these subjects has revealed a strong T-cell response to mesothelin, an immunogenic, tumor-associated molecule that is part of the GVAX vaccine. Furthermore, the data showed the specificity of mesothelin response to be unique in each patient. By contrast, only 1 of the 11 subjects who did not reach the 6.5 year survival mark had mounted any significant mesothelin response, and the level of response was markedly lower. These data were taken to support an ongoing phase II study of GVAX in the disease.<
Erimos Pharmaceuticals announced positive results of their phase I study of EM-1421, their small-molecule tumor-selective chemotherapeutic under investigation for the treatment of refractory head and neck cancer. Trail data showed the drug to be safe and well tolerated, without any observed systemic side effects after three treatments. Preliminary evidence of efficacy was also observed, with visible tumor necrosis noted in 5 of the 6 subjects on the completion of treatment. This open label dose escalation study treated 6 head and neck cancer patients with three intralesional injections of the drug, with a tumor-volume-dependant dosing regimen of 20 mg/cm3; the maximum cumulative administered dose was 1485 mg.
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.
June 14, 2004
Aesgen reported positive results of their phase III study of Saforis (L-glutamine) for the treatment of oral mucositis in cancer patients receiving chemotherapy. Results showed that Saforis significantly reduced the severity and duration of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy regimens versus placebo. Utilizing two sequential treatment cycles, subjects received either Saforis-then-placebo or placebo-then-Saforis. In the first cycle, Saforis subjects showed a 22% reduced incidence of moderate-to-severe oral mucositis, and when this group was switched to placebo during the second treatment cycle, incidence of oral mucositis was 36% below baseline. The multi-center study enrolled 326 evaluable subjects. Based on these results, Aesgen announced plans to file a NDA under their Fast Track designation in the near future.
GlaxoSmithKline reported positive interim results of their phase II study investigating lapatinib, an inhibitor of two receptor tyrosine kinases (ErbB1/EGFR and ErbB2), for the treatment of refractory metastatic breast cancer. Preliminary results from the first 41 subjects indicated that a once daily oral dose of lapatinib might effect an improved or stable disease state in women with breast cancer refractory to standard treatment regimens including Herceptin (trastuzumab). The study found that 46% (n=19) of the evaluated patients had stable or improved disease state at 8 weeks, and 24% (n=10) at 16 weeks. The ongoing multi-center, open label study plans to enroll a total of 80 women with breast cancer over-expressing ErbB2, all of whose disease had been refractory to treatment regimens including Herceptin, an FDA approved monoclonal ErbB2 antibody. If final results confirm the interim analysis, GlaxoSmithKline plans to use this trial to support ongoing trials of lapatinib in multiple ErbB2-expressing solid tumors.
ImClone Systems and Merck KGaA reported negative results from a phase III trial investigating IMC-BEC2, an anti-idiotypic monoclonal antibody cancer vaccine for the treatment of small cell lung cancer (SCLC). Results showed the vaccine trial did not meet its primary endpoint of survival. The international, randomized study was designed to assess the survival benefit of vaccination with IMC-BEC2 and the immune stimulant BCG over a two-year period. Subjects received IMC-BEC2/BCG vaccination or were only monitored in the observation arm. The study was conducted in collaboration with the European Organization for Research and Treatment of Cancer. Both companies intend to meet to discuss the future of the IMC-BEC2 development program.
OncoGenex and Isis announced positive results of a phase I study of OGX-011, an antisense clusterin inhibitor, for the treatment of prostate cancer. Results indicated that the drug achieved high concentration in target tissues and successfully dose-dependently down-regulated the expression of clusterin, a cell survival mediator. The study was designed to assess the bioavailability, tissue specificity and optimum dosing regimen of weekly IV infusions of OGX-011 in subjects with localized prostate cancer over 4 weeks. Immunostaining revealed availability of OGX-011 in the target tissue, and a 91% reduction in clusterin at the highest dose level (640 mg); this dose was determined to be optimum for future studies. The study enrolled a total of 25 subjects eligible for prostatectomy, all of whom underwent the surgery following the trial. OncoGenex and Isis planned to use the dosing information obtained in this trial to support the initiation of a phase II study later this year.
Therion Biologics reported results from two phase I trials investigating PANVAC-VF, a therapeutic cancer vaccine for the treatment of pancreatic cancer. The subcutaneously administered vaccine is designed to stimulate the immune system to target and destroy cancer cells expressing the carcinoembryonic antigen (CEA) and mucin -1 (MUC-1). Results showed a median overall survival of 7.9 months and at least 5.3 months, respectively, compared to an historical median overall survival of approximately 3.0 months. In addition, 33% of subjects in the study remain alive at 13 months. No serious adverse events related to the vaccines were reported. Common side effects included fever, chills and fatigue. The open label studies enrolled a total of 22 subjects with advanced (Stage III or IV) pancreatic cancer who had received prior chemotherapy. Due to these positive results, Therion will conduct a pivotal phase III trial with PANVAC-VF in the summer of 2004.
November 3, 2003
Aphton reported positive results from a phase III trial investigating G17DT, an anti-gastrin targeted immunotherapy for the treatment of pancreatic cancer. Results demonstrated a median survival of 151 days with G17DT compared with 83 days with placebo. Data showed a nine month survival for subjects treated with G17DT was approximately 22% compared with 11% for the placebo group. The randomized, double-blind, placebo-controlled study enrolled 154 subject with advanced pancreatic cancer at 22 sites in Europe. Subjects received G17DT alone or matching placebo. Each were treatment-naive with Stage II, III or IV disease and had a life expectancy of at least 2 months plus a Karnofsky index for performance status (KPS) of greater than or equal to 60%.
January 6, 2003
Isis Pharmaceuticals reported positive results from a phase II trial investigating ISIS 2503 in combination with gemcitabine for the treatment of pancreatic cancer. Results showed 57.5% of subjects who received ISIS 2503, in combination with gemcitabine, survived six months or longer with a median survival time for those 20 subjects of 6.7 months. This was compared to historical gemcitabine pivotal trial results of 46% at six months survival with a median survival time of 5.6 months. The open-label Phase II trial enrolled 48 subjects with locally advanced or metastatic pancreatic cancer who had not received prior chemotherapy for their disease.
Neurocrine Biosciences reported positive results from two trials investigating IL-4 Fusion Toxin (NBI-3001) for the treatment of glioblastoma multiforme and solid tumors. Preliminary data from an ongoing phase I trial conducted in subjects with peripheral solid tumors showed the study has met the primary objectives of defining dose toxicity and tolerance. Two subjects with kidney carcinoma showed stable disease at the maximum tolerated dose. Data from a phase II trial conducted on subjects with glioblastoma multiforme (GBM) showed a median survival greater than six months at low dosage (90 mcg) with the majority of the subjects still alive at time of follow up. MRI scans showed 25% of the subjects reached stable or partial regression of disease. The open label study enrolled 32 subjects with recurrent GBM and infused them intramorally at high, medium and low doses over five days.
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.
April 22, 2002
MGI Pharma has discontinued a phase III trial of Irofulven (MGI-114) for the treatment of gemcitabine-refractory pancreatic cancer. Irofulven activity was observed in the trial; however, the comparator agent (5-fluorouracil) demonstrated a greater than expected survival benefit, making it statistically improbable that the trial objectives would eventually be achieved. An independent Data and Safety Monitoring Board conducted the preliminary data analysis. While MGI Pharma does not plan to pursue testing of Irofulven specifically for gemcitabine-refractory pancreatic cancer, the company will continue with the overall development program.
March 11, 2002
Phase II trial results suggest that Pharmacias Camptosar (irinotecan) plus gemcitabine may be more effective in treating advanced pancreatic cancer than gemcitabine alone. Treatment with the combination therapy produced a one-year survival rate of 27%, which is greater than that reported with gemcitabine alone in previous studies. The 45-subject, multicenter, open-label trial evaluated Camptosar plus gemcitabine in subjects with previously untreated unresectable or metastatic pancreatic cancer. The median survival from the trial was 5.7 months, and subjects also experienced a favorable tumor response rate compared to conventional rates from single agent therapy.