February 16, 2016
Novocure has released results of a phase
III study of Tumor Treating Fields (TTFields)
in combination with temozolomide in newly
diagnosed glioblastoma (GBM). Novocure’s
phase III pivotal trial compared TTFields therapy
in combination with temozolomide to temozolomide
alone in 695 patients with newly
diagnosed GBM. The trial met its endpoints at
the interim analysis. The trial’s results demonstrated
superior progression-free and overall
survivals in patients receiving TTFields therapy
in combination with temozolomide compared
to temozolomide alone (median progression-free
survival of 7.2 months compared to 4
months, hazard ratio=0.62, p=0.001; median
overall survival of 20.5 months compared to
15.6 months, hazard ratio=0.66, p=0.004). In
October 2015, the FDA approved Optune—a
portable, non-invasive device that delivers
TTFields—in combination with temozolomide
for the treatment of adult patients with newly
diagnosed glioblastoma. TTFields are the first
FDA-approved therapy in more than a decade
to demonstrate statistically significant extension
of overall survival in newly diagnosed
GBM, with a two-year survival of 48% versus
32% compared to temozolomide alone.
December 9, 2013
Threshold Pharmaceuticals issued results
of a phase I trial of TH-302 in combination
with Avastin (bevacizumab) in patients with
recurrent glioblastoma following bevacizumab
failure. No dose-limiting toxicity has
been reported to date at doses of TH-302 up
to 670mg/m2 plus bevacizumab at 10mg/m2
every two weeks. A total of 19 patients have
been enrolled in the ongoing trial. Of 14
patients evaluable for tumor response, the
median time to progression was 86 days.
46% (95% CI: 18%-74%) of patients were
alive without disease progression after three
months of treatment. Preliminary data in 14
patients showed TH-302 in combination with
bevacizumab was associated with a median
time to progression of 2.8 months. One patient
achieved a complete response and two
patients achieved partial responses. No grade
4 adverse events were observed at any dose.
Two grade 3 adverse events were observed at
340mg/m2 and 670mg/m2 of skin ulceration
and thrombocytopenia, respectively. The
study is continuing to enroll patients.
May 13, 2013
Agenus released preliminary results from a phase II trial of Prophage G-100 (HSPPC-96) for glioblastoma multiforme (GBM). This single-arm study enrolled 46 patients with newly diagnosed GBM. Subjects received the HSPPC-96 vaccination, as well as radiation and temozolomide as the standard of care. Results showed patients treated with the HSPPC-96 arm showed a 146% increase in progression-free survival (PFS) over standard of care alone (17 months versus 6.9 months, respectively) and a 60% increase in overall survival (OS) over standard of care alone (23.3 months versus 14.6 months, respectively). In addition, 32 patients treated at UCSF underwent testing for expression of B7-H1 in blood samples taken prior to surgery, which showed patients with low expression of B7-H1 (53%) had better PFS (21.6 months) than those with high B7-H1 (47%) expression (11.4 months). This finding may have the potential to help identify a more responsive patient population for future trials.
April 22, 2013
Activartis reported preliminary results from a phase II trial of AV0113 for the treatment of glioblastoma multiforme (GBM). This multi-center, randomized, placebo-controlled study had enrolled 100 subjects with GBM at the time of analysis. Subjects received standard first-line therapy, plus AV0113 DC-CIT inoculated into inguinal lymph nodes: after six weeks of chemo and radiotherapy, four weekly applications; six more applications every four weeks; and then one boost immunization every three months. Preliminary results revealed a very promising trend suggesting an overall survival benefit of patients in the AV0113 treatment group compared to the randomized control group. At 12 months, 64% of patients in the treatment group and 48% of patients in the control group were still alive. At 18 months, 50% of patients in the treatment and 33% of patients in the control group were still alive. Patients receiving AV0113 cancer immunotherapy tended to experience signs of relapse earlier compared to control patients. AV0113-triggered inflammation in the tumor tissue may explain this observation, which was also made in other clinical trials studying cancer immunotherapy. AV0113 treatment was well tolerated. The most frequent adverse events were local swelling, redness and tenderness at the injection site. Activartis will continue the phase II trial to confirm the observed trend.
March 12, 2012
Apogenix GmbH released initial results from a phase II trial of APG101 for the second line treatment of Glioblastoma Multiforme. This open-label, randomized, controlled study enrolled 83 subjects with first or second relapse. The subjects received APG101 plus radiotherapy versus radiotherapy alone. The primary objective of the trial was to increase the percentage of subjects reaching a six month rate of progression free survival (PFS6) by 100%. This objective was reached. During treatment with APG101 for up to two years, no drug-related adverse effects were observed.
September 19, 2011
Immunocellular Therapeutics reported long term results from a phase I trial of ICT-107, their cancer vaccine candidate for the treatment of glioblastoma multiforme. The study enrolled 16 subjects with newly diagnosed glioblastoma who received three injections of ICT-107 in addition to standard treatment with surgery, radiation and chemotherapy. Three-year overall survival is 55% compared to 16% for historical standard of care (SOC). The data show that 38% of subjects who received ICT-107 continue to show no tumor recurrence after three years, compared to the historic disease-free survival rate of 6% with SOC. Out of these subjects, 19% remain disease-free after more than four years. The three-year median overall survival (OS) for subjects receiving ICT-107 is currently 38.4 months, and median progression-free survival (PFS) is 17 months. This historical median OS is 14.6 months and PFS is 6.9 months with SOC.
November 29, 2010
Celldex issued results from a phase II trial of rindopepimut, an immunotherapeutic vaccine under investigation for glioblastoma multiforme (GBM). This open label trial, ACT III, enrolled 65 subjects with newly-diagnosed EGFRvIII-expressing GBM who had undergone surgical resection followed by radiation therapy, temozolomide (TMZ) without tumor progression. Rindopepimut mixed with granulocyte-macrophage colony stimulating factor (GM-CSF) (~150 mcg) was administered intradermally bi-weekly for three doses prior to starting maintenance TMZ and monthly thereafter on day 21 of each TMZ cycle until disease progression. The results for the predefined primary endpoint (66% Progression Free Rate at approximately 8.5 months post-diagnosis) show a statistically significant improvement (p≡0.0168) over a predetermined estimate of 53%, which is beyond the range of expected progression-free survival for treatment with standard of care, consisting of radiation plus TMZ. In addition, 82% of the evaluable population developed a specific anti-EGFRvIII antibody response that was maintained at a significant level. Vaccination with rindopepimut plus TMZ was well tolerated.
May 25, 2009
Exelixis issued positive interim results from a phase II trial of XL184 for the treatment of glioblastoma multiforme. This open-label, uncontrolled trial planned to enroll 46 subjects who were to receive daily XL-184 (25 or 100 mg gelatin capsules). The primary endpoint was the 6-month progression-free survival rate. Data are from 26 subjects who were assessed at four weeks after treatment. Ten of the subjects (38%) had tumor shrinkage of at least 50 percent, including one who had a 100 percent reduction in tumor size. Nine subjects had tumor measurement changes ranging from plus 24% to minus 49% and seven had at least a 25 percent increase in tumor burden. Of 17 subjects who had not received prior anti-angiogenic treatment, nine had at least a 50 percent reduction in tumor burden.
February 25, 2008
Cell Genesys reported positive results from a phase II trial of GVAX for the treatment of prostate cancer. The analysis was designed to evaluate the potential association between immune responses to GVAX and increased survival. The study enrolled eighty subjects, sixty five of whom had their serum evaluated to determine each subjects' immune response to two specific antigens, HLA-A24 and FLJ14668, following GVAX treatment. Of the sixty five subjects, thirty four demonstrated an FLJ14668-specific antibody immune response and had a median survival of forty three months. The median survival of subjects who did not generate the anti-FLJ14668 antibodies was twenty one months (p=0.002). Twenty-two of these sixty five subjects received a dose of GVAX comparable to that being evaluated in ongoing phase III prostate cancer trials. Of these twenty two subjects, sixteen (73%) mounted an immune response to FLJ14668. These sixteen subjects achieved a median survival of 44.9 months. The median survival for all twenty two subjects in this treatment group was thirty five months. Of the fifty eight subjects who were HLA-A24 genotype negative and therefore potentially able to mount anti-HLA-A24 specific antibody responses, thirty subjects were found to be anti-HLA-A24 antibody positive. These thirty had a median survival of forty three months, compared to a median survival of eighteen months in the subjects who did not generate anti-HLA-A24 antibodies (p=0.05). Phase III trials are currently underway.
Northwest Bio announced long-term follow-up data from phase I and phase I/II trials of DCVax-Brain for the treatment of Glioblastoma multiforme (GBM). Data is from 19 subjects with newly diagnosed Glioblastoma multiforme who received surgery followed by DCVax-Brain plus standard of care (a combination of radiation and daily Temodar chemotherapy and then 6 monthly cycles of Temodar chemotherapy). Eight of 19 subjects were still alive (ranging from 24.5 months to 92 months), with median overall survival in all subjects of 33.8 months compared to 17 months in subjects who received standard of care alone (p < 0.0079). Five of the 8 subjects who were still alive showed no signs of cancer recurrence, with follow-up time ranging from 41 months to 92 months. The median time to progression was 18.1 months, compared to 8.1 months for subjects receiving standard of care alone (p = 0.00001). To date, 68% of subjects receiving DCVax-Brain in addition to Standard of Care have lived longer than 2 years, 42% have lived longer than 3 years, and 26% have lived longer than 4 years (48, 54, 57, 62 and 92 months so far). Phase II trials of DCVax-Brain are currently underway.
OncoGenex issued positive interim results from a phase II trial of OGX-011 for the treatment of prostate cancer. This open-label, randomized, multicenter study evaluated 43 subjects who received OGX-011 in combination with docetaxel or mitoxantrone, administered as second-line chemotherapy. The subjects underwent a median of 6 cycles of mitoxantrone or 7.5 cycles of docetaxel. To date, with a median follow-up of 13.3 months, in both arms of the trial approximately 30% of subjects have not manifested disease progression and approximately 60% of subjects are alive. Median survival has not been reached in either arm. Reductions in pain or analgesic use were seen in 50% of evaluable subjects treated with mitoxantrone and in 67% of evaluable subjects treated with docetaxel. Based on the results, a phase III trial design is underway.
November 26, 2007
Genentech reported positive results from a phase II trial of Avastin for the treatment of glioblastoma multiforme (GBM). This open-label, multicenter, randomized, non-comparative study enrolled 167 subjects with GBM whose cancer had relapsed after first- or second-line therapy, all of whom had received prior temozolimide. The subjects were randomized to receive Avastin alone or in combination with irinotecan every other week for up to 104 weeks. The primary endpoints were six-month progression free survival (PFS) and objective response rate. The PFS rates were 36% and 51% in the Avastin-alone and Avastin plus chemotherapy arms, respectively. Preliminary tumor responses were observed in 21% of the Avastin alone arm and in 34% of the Avastin plus chemotherapy arm. Treatment was generally well tolerated. Based on the data Genentech plans to meet with the FDA in order to determine the next step of action towards regulatory filing.
February 12, 2007
Adnexus released announced positive interim results from a phase I trial of Angiocept for the treatment of cancer. This open label, dose escalation trial was designed to assess the safety, tolerability and pharmacokinetics of the drug in cancer subjects as well as to evaluate preliminary anti-tumor and biological activity. Interim evidence revealed that within four hours of drug administration biological activity occurred, as evidenced by elevated plasma levels of biomarkers of VEGFR-2 pathway. These biomarkers remained significantly elevated above baseline throughout the multi-dose treatment duration. Pharmacokinetic data demonstrated a profile that could support an every other week dosing regimen. The maximum tolerated dose has not been reached. Based on the results, the development of Angiocept is to continue for this indication.
Celtic announced negative results from phase III trial, dubbed KSB311R/CIII/001, of TransMID for the treatment of glioblastoma multiforme. This randomized, open-label trial was to include tow sequential trials. The first planned to enroll 323 subjects with non-resectable, progressive or recurrent Glioblastoma Multiforme (GBM) who had failed conventional therapy, in North America, the EU and Isreal. It was designed to compare two intratumoral doses of TransMID to best standard of care in improving overall survival. The trial's primary efficacy endpoint was overall survival time; interim analysis was to occur when 50% of the required events were observed. The interim assessment revealed that the probability of the trial achieving the predefined overall survival rate by the trial end was unlikely to occur. Based on this data, Celtic decided to terminate the development of TRansMID for this or any other indication.
Spectrum released positive results from a pilot phase II trial of EOquin for the treatment of non-invasive bladder cancer. This single-arm, open-label study enrolled 20 subjects who received 4 mg of EOquin in 40 mL of diluent administered via an indwelling catheter that was then clamped for one hour. After an hour the bladder was drained and the catheter was removed. Subjects were assessed for adverse events during the one hour retention and at post-operative days eight and fifteen. Wound healing, assessed by cystoscopy performed at postoperative day 85, and systemic absorption were also evaluated. Treatment was well tolerated and no adverse events occurred on wound healing. In addition, EOquin was not systematically absorbed into the bloodstream when given immediately after surgery. A phase III protocol has been submitted to the FDA for a Special Protocol Assessment (SPA). Spectrum plans to start this trial in mid-2007.
May 16, 2005
Marshall Edwards has reported preliminary results of a phase IIa trial of phenoxodiol, their chemotherapy sensitizer for the treatment of ovarian cancer. Trial data yielded significant evidence of efficacy, with 11% of subjects experiencing complete response, 22% achieving partial response, and 44% experiencing stable disease. Overall adverse events were positive, with no unanticipated toxicities. This open-label study enrolled 40 patients with ovarian tumors refractory or resistant to treatment with taxane or platinum based chemotherapy. Subjects received phenoxodiol in combination with a standard regimen of either carboplatin (n=20) or paclitaxel (n=20). The company indicated that these positive results warranted continuation of the trial with a third cohort of treatment refractory subjects (n=20), who were to receive standard chemotherapy, with the addition of phenoxodiol only following evidence of progression.
NeoPharm reported combined data from 3 phase I trials of cintredekin besudotox (IL13-PE38QQR), for the treatment of glioblastoma multiforme (GBM). Peritumoral convection enhanced delivery of the drug yielded an overall median survival of 44.0 weeks, compared to 28 weeks for current approved therapies; 6 subjects experienced durable, ongoing disease stabilization of 39+ to 190+ weeks (median 89+ weeks) following a single treatment with the drug. Furthermore, optimal catheter placement was seen to markedly extend median survival (51.7 weeks vs. 39.3 weeks for sub-optimal). These open-label studies enrolled a total of 45 patients with recurrent resectable GBM, who received a single peritumoral infusion of the drug following resection. The company indicated that these results would serve to support the design of their ongoing phase III trial of the drug, dubbed "PRECISE".
November 29, 2004
Alteris Therapeutics has announced positive results of a phase I clinical trial of their EGFRvIII peptide therapeutic vaccine, for the treatment of malignant glioma. Results from the trial met their primary safety and tolerability endpoints, with no serious adverse events reported and a favorable tolerability profile. Furthermore, the drug demonstrated significant preliminary evidence of efficacy: 2 patients experienced near-complete remission after vaccination, more than 25% of subjects experienced stable disease state during the study, median overall time to disease progression was 314 days, compared to a historical baseline of I24 days, and median survival time was over 596 days, or about 20 months, compared to a historical baseline of 11-13 months. This open-label safety and efficacy trial enrolled a total of 16 patients with malignant glioma at 1 US site, who received a total of three doses of the trial once every two weeks.
Hybridon has issued positive interim results of a phase I trial of IMOxine, their investigational second-generation immunomodulatory oligonucleotide for the treatment of solid tumors. Results from the 19 subjects completing safety evaluations met primary safety and tolerability endpoints, with no dose-limiting toxicity, a tolerability profile consistent with immune system stimulation, and a manageable adverse event profile including transient hypoxia/dyspnea (n=1), abdominal pain with nausea/vomiting (n=1), and anemia requiring transfusion (n=2). There were 4 early withdrawals, all due to disease progression. Furthermore, results from the 17 subjects completing preliminary efficacy evaluations indicated that the drug produced stable disease state in 53% of patients (n=9) after 8 weeks of treatment, and 1 of these subjects maintained this state into the 11th month of treatment. This open-label, open-duration safety and immunpharmacology study enrolled 23 patients with assorted refractory solid tumors at 1 US site. Subjects received IMOxine via weekly subcutaneous injection at one of 5 dosing regimens (0.04, 0.16, 0.32, 0.48, or 0.64 mg/kg).
Pharmacyclics announced the combined results of two phase I trials of Xcytrin (motexafin gadolinium) in combination with cranial irradiation for the treatment of glioblastoma multiforme (GBM). Data from both trials indicated that the duration-ranging regimens met primary safety and tolerability endpoints, with no drug related interruptions of radiation therapy and a manageable adverse event profile which included numbness, tingling and rash of fingertips, nausea and mild diarrhea, and reversible hepatic chemistry abnormalities. Preliminary evidence indicates that the drug promoted improvements in survival. Specifically, patients receiving a cumulative dose >60 mg/kg of Xcytrin experienced a median survival time of 11.5 months, with 82% alive at 6 months and 46% at 12. Patients a cumulative dose <60mg/kg experienced median survival of 16.4 months, with 93% and 78% alive at 6 and 12 months. Overall median survival for the entire group of patients was 14.7 months, with 91% and 69% alive at 6 and 12 months. Both trials were open-label, cumulative-dose-escalation studies (40-117 mg/kg), which enrolled a combined total of 55 subjects with treatment-naïve GBM.