The following data were revealed at the American Society of Clinical Oncology meeting in Chicago.
Abraxis BioScience Inc., of Los Angeles, said results from its Phase III trial of Abraxane (paclitaxel albumin protein-bound particles for injectable suspension) plus carboplatin showed a statistically significant 31 percent improvement in overall response rate when compared with New York-based Bristol-Myer Squibb Co.'s Taxol (paclitaxel) plus carboplatin in the first-line treatment of patients with non-small-cell lung cancer. Patients in the Abraxane arm demonstrated an ORR of 33 percent compared with those receiving Taxol, with an ORR of 25 percent, as assessed by independent radiologic review using RECIST criteria. The firm said the difference met statistical significance at a "p" value of 0.005 and achieved the primary endpoint under a special protocol assessment agreement with the FDA. An analysis of the subset of squamous cell carcinoma showed a 67 percent improvement in those who received the Abraxane combination vs. those who received the Taxol combination.
AEterna Zentaris Inc., of Quebec City, said Phase II results showed that five of 42 patients, or 11.9 percent, with platinum-resistant ovarian cancer had a partial response after receiving AEZS-108, and 11 patients, or 26.2 percent, had stable disease for more than 12 weeks, for an estimated clinical benefit rate of 38 percent. The median time to progression and overall survival were 3.5 months and 15.6 months, respectively. The firm said AEZS-108 was well tolerated, with only one patient experiencing a dose reduction. Separately, the company reported that Phase I data of perifosine (KRX-0401) in recurrent pediatric solid tumors showed no dose-limiting toxicity at any of the three dose levels, and PK data so far suggest similar drug absorption by pediatric patients relative to adults. Perifosine is partnered with New York-based Keryx Biopharmaceuticals Inc. Shares of AEterna Zentaris (NASDAQ:AEZS) fell 18 cents, or 10.6 percent, to close Monday at $1.52, while shares of Keryx (NASDAQ:KERX) lost 58 cents, or 12 percent, to close at $4.22.
Alder Biopharmaceuticals Inc., of Bothell, Wash., said Phase IIa results showed that patients with late-stage non-small-cell lung cancer had improvement in cancer-related anemia and symptoms of the disease after receiving ALD518, a monoclonal antibody directed against interleukin-6. After 12 weeks of treatment with the anti-inflammatory therapeutic, 58 percent of patients experienced hemoglobin level increases from less than 11 g/dL to more than 12 g/dL, while no patients receiving placebo experienced the increase. In addition, patients who received ALD518 had an average lean body mass loss of 0.19 kg, compared with an average loss of 1.5 kg in those who received placebo. Additional symptoms of the disease, such as fatigue, also were reduced in the ALD518 arm.
Allos Therapeutics Inc., of Westminster, Colo., said new analyses of data from its pivotal PROPEL trial demonstrated that patients with relapsed or refractory peripheral T-cell lymphoma who responded to Folotyn (pralatrexate injection) had up to a 44 percent reduction in risk of death based on independent central review of response and up to a 56 percent reduction in risk of death based on investigator review of response, compared with those who did not respond to the drug.
Alnylam Pharmaceuticals Inc., of Cambridge, Mass., said preliminary data from its ongoing Phase I trial from the initial 19 patients in the first four-dose cohorts demonstrated that ALN-VSP was well tolerated in most patients, with pharmacodynamic measurements providing preliminary evidence of clinical activity. The firm noted that the study has not yet reached a maximum-tolerated dose and is continuing enrollment with dose escalation.
Amgen Inc., of Thousand Oaks, Calif., said new integrated analyses of two Phase III studies showed that Prolia (denosumab) was superior over Basel, Switzerland-based Novartis AG's Zometa (zoledronic acid) in delaying or preventing skeletal-related events (SREs) in broad population with advanced cancer. Prolia delayed the time to first on-study SRE over Zometa and delayed the time to first-and-subsequent SREs. Amgen said its drug also reduced the mean skeletal morbidity rate vs. Zometa, 0.64 compared with 0.80. Amgen also said detailed results from a head-to-head Phase III trial demonstrated that Prolia was superior to Zometa in significantly delaying the time to first on-study SRE in patients with hormone-refractory prostate cancer and bone metastases, with a median time of 20.7 months vs. 17.1 months, respectively. In a separate presentation, Amgen reported that AMG 386, a peptibody designed to inhibit angiopoietin-1 and -2, demonstrated antitumor activity when combined with paclitaxel in a randomized Phase II trial involving 161 patients with recurrent ovarian cancer. Median progression-free survival, the study's primary endpoint, in the 10 mg/kg arm was 7.2 months vs. 5.7 months in the 3 mg/kg arm and 4.6 months in the placebo group.
Angiochem Inc., of Montreal, said data from two Phase I/II trials of ANG1005 showed that overall disease control was achieved in 71 percent of patients dosed at or above 420 mg/m2, including 10 patients who failed prior taxane therapy. Partial responses were observed in five patients at maximum-tolerated dose, with two patients having breast cancer, two with non-small-cell lung cancer and one with ovarian cancer. The firm said important reductions in the size of cancer tumors also were achieved in metastases located in organs outside of the brain including the liver, lung and lymph nodes. Median time to progression was 18 weeks in responders and eight weeks in all patients.
Antisoma plc, of London, said an analysis of Phase II data showed comparable activity with AS1413 plus cytarabine in the two subgroups of secondary acute myeloid leukemia patients being studied in the ongoing Phase III trial, which includes patients with prior myelodysplastic syndrome and patients previously treated for other cancers. Separately, follow-up data of the AS1411 Phase II trial in relapsed/refractory AML showed durable remissions among patients who responded to the drug in combination with cytarabine.
Ariad Pharmaceuticals Inc., of Cambridge, Mass., said updated data from an ongoing Phase I study confirmed strong clinical evidence of hematologic, cytogenetic and molecular anti-leukemia activity of AP24534, a multitargeted kinase inhibitor, in heavily pretreated patients with chronic myeloid leukemia, including those with the T315I mutation of the target protein Bcr-Abl.
ArQule Inc., of Woburn, Mass., and Daiichi Sankyo Co. Ltd., of Tokyo, said data from a Phase II trial in patients with advanced, refractory non-small-cell lung cancer demonstrated a median overall survival in the intent-to-treat population of 36.6 weeks for the ARQ 197 plus Tarceva (erlotinib, OSI Pharmaceuticals Inc. and Roche AG) arm compared with 29.4 weeks in the erlotinib plus placebo arm, an improvement of 24 percent. In the predefined subgroup of patients with nonsquamous cell carcinoma histology, the median overall survival was 43.1 weeks in the treatment arm, compared with 29.4 weeks in the placebo arm, an improvement of 47 percent. As previously reported, the ARQ 197 plus erlotinib combination demonstrated a 66 percent improvement in the primary endpoint, median progression-free survival, although the difference in PFS between the two arms did not achieve statistical significance. Improvement in median PFS was more pronounced in the predefined subgroup of patients with nonsquamous histology. Shares of ArQule (NASDAQ:ARQL) dropped 16.2 percent, or 91 cents, to close Monday at $4.70. (See BioWorld Today, April 1, 2010.)
AstraZeneca plc, of London, said results from its Phase III ZETA study in patients with advanced medullary thyroid cancer showed that treatment with vandetanib significantly extended progression-free survival, the primary endpoint of the study, by demonstrating a 54 percent reduction in the rate of progression compared to placebo.
AVEO Pharmaceuticals Inc., of Cambridge, Mass., said data from a subgroup analysis of a Phase II trial of tivozanib, an inhibitor of VEGF receptors 1, 2 and 3, showed a median progression-free survival of 14.8 months in patients with advanced clear cell renal-cell carcinoma who had undergone prior nephrectomy. PFS was similar between patients who were treatment-naïve and those who had received prior therapy with cytokines and/or chemotherapy. Median PFS among all 272 patients in the trial was 11.8 months. The company also said results of a Phase I trial of SCH 900105, an antibody targeting hepatocyte growth factor/scatter factor (HGF/SF), showed good tolerability with no dose-limiting toxicities up to the highest dose tested, 20 mg/kg.
BioTheranostics, of San Diego, reported findings from clinical studies using the company's CancerTYPE ID and Breast Cancer Index molecular oncology tests. While prior studies of CUP patients with empirical chemotherapy have shown median survival of seven months on the low end and 11 months on the high end, interim findings from the UNKPRI20 study suggested that selecting treatment based on results from the CancerTYPE ID assay leads to median survival of 12.9 months.
Bristol-Myers Squibb Co., of New York, and Otsuka Pharmaceutical Co. Ltd., of Tokyo, reported Phase III study results in which Sprycel (dasatinib) 100 mg once daily demonstrated a superior rate of confirmed complete cytogenetic response (CCyR) compared to Gleevec (imatinib mesylate). The study, known as DASISION, compared Sprycel vs. Gleevec as a first-line treatment for patients with chronic phase chronic myeloid leukemia (CML-CP). In the study, 77 percent of Sprycle patients vs. 66 percent of Gleevec patients achieved confirmed CCyR (two consecutive assessments of CCyR) by 12 months (p = 0.007). BMS and Otsuka are in the process of submitting the DASISION data to worldwide health authorities this year for the approval of Sprycel as a first-line treatment for newly diagnosed adult patients with CML-CP.
Calistoga Pharmaceuticals Inc., of Seattle, presented updated data on CAL-101, its oral, delta selective PI3K inhibitor, showing antitumor activity in patients with hematologic malignancies treated during a Phase I trial. Single agent CAL-101 treatment in patients with relapsed or refractory indolent non-Hodgkin's lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia resulted in overall response rates of 57 percent, 67 percent, and 30 percent, respectively. Furthermore, 94 percent of patients with CLL had greater than 50 percent decrease in their lymph node disease, demonstrating a high degree of biologic activity. The majority of responding patients remain on CAL-101 treatment.
Celator Pharmaceuticals Inc., of Princeton, N.,J., reported a subset analysis of data from its Phase II study in newly diagnosed acute myeloid leukemia (AML), showing that CPX-351 (cytarabine:daunorubicin) liposome injection can induce complete remissions in patients following the failure of induction therapy with conventional cytarabine and daunorubicin (the "7+3" regimen). In the study, 10 of the 41 patients in the "7+3" arm experienced primary induction failure and were subsequently treated with CPX-351. In this group, four patients (40 percent) experienced complete remissions, including one CR and three complete remission with an incomplete recovery, to a specified level, of neutrophils and/or platelets. Two of six patients with secondary AML, and two of four de novo AML patients achieved a remission. The primary efficacy endpoint analysis, and additional results from the study, will be submitted to a major medical conference this year.
Celldex Therapeutics Inc., of Needham, Mass., reported interim results from a Phase IIb study evaluating rindopepimut (formerly PF-04948568 or CDX-110) in newly-diagnosed glioblastoma multiforme patients. Some 70 percent of ACT III patients were progression-free at 5.5 months after initiating treatment with rindopepimut. The final ACT III data are expected later this year. Celldex also reported mature results from a Phase I/II study evaluating CDX-011 in advanced stage breast cancer patients. Mature data showed a progression-free survival rate at 12 weeks of 35 percent of patients. A Phase IIb trial in advanced, refractory breast cancer is planned, which will select patients on the basis of significant GPNMB expression. The company also reported that updated Phase II study results of Opaxio (paclitaxel poliglumex) in patients with advanced esophageal cancer demonstrated that 38 percent (15/40) of patients receiving Opaxio in combination with cisplatin and concurrent radiation achieved a pathologic or endoscopic complete response. Shares of Celldex (NASDAQ:CLDX) fell $1.42, or 21.7 percent, closing at $5.14.
ChemGenex Pharmaceuticals Ltd., of Melbourne, Australia, reported positive safety findings from a combined analysis of two clinical trials for its lead product candidate, Omapro (omacetaxine mepesuccinate). The primary toxicity is hematologic, with infrequent grade 3/4 nonhematologic events experienced. The events were manageable and decreased in frequency and severity with dose adjustments. And injection site reactions were primarily grade 1/2 events, demonstrating that at-home subcutaneous administration of omacetaxine has an acceptable safety profile for CML patients who have failed prior therapies.
Chronix Biomedical, of San Jose, Calif., reported new data demonstrating that its DNA blood tests can accurately detect early stage breast and prostate cancers by identifying disease-specific fingerprints based on DNA fragments released into the blood stream by damaged and apoptotic cells. In the 575-subject study, Chronix's assays detected and identified DNA fingerprints in the blood that indicated the presence of prostate or breast cancers with 92 percent specificity and 100 percent specificity.
Delcath Systems Inc., of New York, reported positive Phase III results comparing percutaneous hepatic perfusion (PHP) with melphalan to the best alternative care for patients with hepatic metastases from ocular or cutaneous melanoma. PHP patients showed median hepatic progression-free survival (hPFS) of 245 days compared to 49 days in the BAC arm, a 5x extension of hPFS. Median overall survival in the PHP arm was 298 days, compared to median overall survival of 124 days for those patients in the BAC arm who did not cross over. The hepatic response rate in the PHP arm was 34.1 percent compared to 2 percent for the BAC arm and 22.2 percent for patients who crossed over to receive PHP upon progression of their tumors. In the PHP arm 52.3 percent of patients achieved stable disease, compared with 26.5 percent in the BAC group, and 40.7 percent in the crossover group.
Eisai Co. Ltd., of Tokyo, said results of a Phase III study showed eribulin mesylate significantly improved median overall survival (OS) compared with Treatment of Physician's Choice (TPC) in heavily pre-treated metastatic breast cancer patients. The Phase III EMBRACE study met its primary endpoint of overall survival, showing that patients who received eribulin survived a median of 2.5 months longer than patients who received TPC (overall survival of 13.12 months vs. 10.65 months, respectively, p = 0.04). Results from EMBRACE also showed that a secondary endpoint of overall response rate was statistically significant. Another secondary endpoint, progression-free survival, was supportive of the primary endpoint but did not reach statistical significance.
Endocyte Inc., of West Lafayette, Ind., said an interim analysis from a Phase II trial in women with platinum-resistant ovarian cancer indicated that EC145 plus Doxil (doxorubicin liposomal) doubled the median progression-free survival compared to Doxil alone, increasing from about three months to six months (hazard ratio of 0.497; "p" value of 0.014). The preliminary overall survival analysis also indicated a trend toward benefit in the EC145 arm (hazard ratio of 0.425; "p" value of 0.064). The interim analysis was based on data from 91 women. EC145 is a conjugate of the vitamin folate and a vinca alkaloid.
Exelixis Inc., of South San Francisco, reported updated interim data from three ongoing trials of XL147 (SAR245408), an orally available small-molecule inhibitor of phosphoinositide-3-kinase (PI3K). Data included interim results from an ongoing Phase Ib/II study of XL147 in combination with erlotinib in patients with advanced solid tumors. Twenty-six patients were evaluable for tumor response. One with NSCLC who had prior chemotherapy but was erlotinib-naive achieved a partial response and a 59 percent decrease of metastatic disease after cycle three, with a 24-week duration of response. Seven additional patients had SD greater-than or equal to eight weeks, four of which remained on treatment for greater than or equal to 24 weeks. Most adverse events were grade 1 or 2 in severity. Exelixis also reported updated interim data from three ongoing trials of XL765 (SAR245409), an orally available small-molecule inhibitor of phosphoinositide-3-kinase and mTOR. Interim results from an ongoing Phase I dose-escalation trial in patients with advanced malignancies showed that 12 patients had been on treatment for greater than or equal to 16 weeks with seven patients remaining on treatment for greater-than or equal to 24 weeks. XL765 administered qd or bid was generally well tolerated. Most adverse events were grade 1 or 2 in severity.
Genomic Health Inc., of Redwood City, Calif., presented the results of six studies, including an evaluation of biological similarities and differences between stage II and III colon cancer, suggesting a potential role for its Oncotype DX colon cancer test in patients with stage III disease, pending further study. Some tumor characteristics, such as grade, and a small number of individual genes were identified that may distinguish stage II and III colon cancers, but there is a striking similarity between the two stages for the vast majority of the 375 genes studied and for the 12-gene Oncotype DX colon cancer Recurrence Score, the firm said.
Genta Inc., of Berkeley Heights, N.J., presented results from two dose-ranging trials of tesetaxel, its oral tubulin inhibitor, showing potential activity in patients with taxane-resistant cancers, along with no evidence of hypersensitivity and a low incidence of nerve damage. A single oral 40-mg dose was established for ongoing and future studies, with incremental escalation depending on individual tolerance. Accrual to the weekly schedule is ongoing, and final determination of a maximally tolerable weekly dose is pending.
Geron Corp., of Menlo Park, Calif., presented positive data from the clinical trial of imetelstat (GRN163L), a telomerase inhibitor drug, in combination with paclitaxel and bevacizumab in patients with breast cancer. The preliminary data confirmed overall response rate was 53.8 percent (95 percent confidence interval: 28.7 percent to 77.6 percent) based on investigator assessment of disease status using the Response Evaluation Criteria in Solid Tumors. Median duration of response was 21.7 weeks (7.3 to 48.3 weeks). Pharmacokinetic profile of imetelstat in combination therapy with paclitaxel and bevacizumab was comparable to the PK profile of imetelstat administered alone (from the Phase 1 trial in solid tumors). In the solid tumor trial, the observed level of exposure to imetelstat during the treatment period was higher than the exposure that was associated with inhibition of telomerase activity and tumor growth in multiple xenograft animal models of human cancers. Similarly, in the Phase I combination trial in breast cancer, modeled AUC values at doses of imetelstat from 240 mg/m(2) and above also exceeded the exposure required for efficacy in preclinical models.
GTx Inc., of Memphis, Tenn., said additional results from the Ostarine Phase IIb study demonstrated an improvement in the quality of life (fatigue and anorexia) in patients with cancer cachexia who showed improvement in functional performance as measured by the stair climb. Patients in the 16-week trial treated with Ostarine, a selective androgen receptor modulator, were more likely than the placebo group to demonstrate an improvement in stair climb time (58 percent vs. 22 percent) and stair climb power (47 percent vs. 31 percent) and also showed statistically significant improvements in fatigue and anorexia scales when compared to patients with no improvements in stair climb speed or power.
Hana Biosciences Inc., of South San Francisco, presented complete data from its pivotal, Phase II RALLY trial for Marqibo (vincristine sulfate liposome injection) for the treatment of relapsed/refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL), which it said showed compelling evidence of single-agent, anti-leukemic activity in an advanced, heavily pre-treated, adult ALL population. An analysis of the 65 evaluable subjects demonstrated an overall response in 35 percent and a complete response with incomplete blood count recovery in 20 percent of the subjects. The estimated median overall survival in complete responders was 7.4 months, with five patients having an overall survival greater than one year. The estimated median duration of CR/CRi was 5.3 months. Ten patients treated with Marqibo went on to receive a potentially life-saving stem cell transplant. There were no unexpected toxicities.
Harbor BioSciences Inc., of San Diego, reported new data from its ongoing Phase I/IIa trial of Apoptone (HE3235) in castration-resistant prostate cancer, specifically results from the 100 mg cohort of chemotherapy-naïve patients indicating a median time to progression of greater than 16 weeks, with 80 percent remaining on treatment. Additional data showed that, of 28 evaluable taxane-resistant prostate cancer patients, 16 (57 percent) had stable disease or improvement of metastatic soft-tissue and/or bone lesions by imaging and have received one to eight additional treatment cycles before disease progression. Apoptone is a steroid analogue of a testosterone metabolite. Shares of Harbor (NASDAQ:HRBR) fell 13 cents, or 30 percent, to close Monday at 30 cents.
Immatics Biotechnologies GmbH, of Tuebingen, Germany, said Phase II results with its therapeutic cancer vaccine IMA901, or cyclophosphamide (CY) in patients with advanced renal cell carcinoma showed a strong signal for improved survival and excellent safety profile. Patients randomized to receive a single dose of showed a strong trend toward improved overall survival vs. patients who did not receive CY (p = 0.086; median OS not reached after 23 months of follow-up in the CY-pretreated patients vs. median OS of 16 months in the other patients). The survival data compared favorably to previous studies of the approved tyrosine kinase inhibitors sunitinib and sorafenib, the company said. Immatics plans to start a randomized, controlled pivotal clinical trial with IMA901.
ImmunoGen Inc., of Waltham, Mass., presented the first clinical data for the IMGN388 anticancer compound showing that in the dose-escalation trial it demonstrated favorable tolerability at the dose levels evaluated to date, and evidence of activity is being reported now that higher doses are starting to be evaluated. Dose escalation is continuing. IMGN388 is in development for the treatment of solid tumors using the company's Targeted Antibody Payload technology and consists of the firm's DM4 cancer-cell killing agent attached to an av integrin-targeting antibody. The company also announced the presentation of data from a Phase Ib/II trial by Roche and Genentech on the safety and preliminary efficacy of trastuzumab-DM1 used in combination with Roche's investigational antibody, pertuzumab supporting the tolerability profile of compounds made with ImmunoGen's Targeted Antibody Payload technology.
Incyte Corp., of Wilmington, Del., reported additional positive results from an ongoing Phase I/II trial for its selective oral sheddase inhibitor INCB7839 involving 66 patients with HER2-positive metastatic breast cancer. Study results suggested that, when treated with a combination of INCB7839 and trastuzumab, the subset of patients with p95HER2-positive metastatic cancer showed clinical benefit in terms of overall response rate and progression-free survival when compared to the p95HER2-negative patients.
Infinity Pharmaceuticals Inc., of Cambridge, Mass., reported Phase II results showing that IPI-504, an intravenously administered Hsp90 chaperone inhibitor, demonstrated clinical activity in patients with non-small-cell lung cancer, in particular among those with oncogenic anaplastic lymphoma kinase gene rearrangements. Results of the 76-patient trial showed an objective response rate of 7 percent in the overall study population. In a subset of patients who underwent genotyping analysis, the response rate was 10 percent for those who were EGFR wild-type, 4 percent for those with EGFR mutations and 12 percent for those with KRAS wild-type mutations. Infinity also reported supporting in vitro data demonstrating that the ALK rearrangement protein is a sensitive client of Hsp90 and that IPI-504 induced degradation of ALK, thereby inhibiting downstream signaling pathways.
Merck Serono, a division of Merck KGaA, of Darmstadt, Germany, reported positive long-term follow-up data of a randomized Phase II study of two cilengitide doses in recurrent glioblastoma. The data showed that treatment of 15 patients with the investigational integrin-inhibitor for more than six months and for up to 4.5 years did not result in any treatment-related severe adverse events (Grade 3/4). In addition, 37 percent of patients who received the higher dose of cilengitide (2,000 mg) were still alive after one year and 22 percent after two years. The current prognosis of patients with recurrent glioblastoma is between four months and seven months and one-year survival rates of approximately 20 percent.
MethylGene Inc., of Montreal, reported preliminary data showing that mocetinostat, an oral, isotype-selective histone deacetylase inhibitor, has resulted in one patient with a complete response rate and two additional patients with partial responses, for an overall objective response rate of 11 percent. In addition, 20 patients were evaluated by CT scan, showing that 13 (65 percent) experienced tumor shrinkage. The study has enrolled 28 patients with relapsed or refractory follicular lymphoma. In a separate presentation, MethylGene disclosed additional data, including preliminary Phase I data showing that MGCD265, a c-Met kinase inhibitor, in advanced metastatic or unresectable malignancies has resulted in stable disease for 10 of 22 evaluable patients (45 percent), with five patients (23 percent) remaining on study for four cycles or more. Shares of MethylGene (TSX:MYG) closed at C22 cents (US21 cents), down C4 cents, or 13.7 percent.
Micromet Inc., of Bethesda, Md., presented updated interim results from a Phase I trial of the company's BiTE antibody MT110 in patients with advanced solid tumors. Out of 22 patients evaluable for response, disease stabilization was observed in nine patients, with a median duration of 91 days. Investigators observed redistribution and expansion of T cells in blood, and infiltration of T cells into tumor tissue. The majority of adverse events were Grade 1 and 2. Transient increases in liver laboratory parameters have been observed in the majority of patients at the start of treatment. A new dosing schedule was implemented to reduce the liver enzyme levels at the onset of treatment. To date, no maximum tolerated dose has been reached and dose escalation continues.
Millennium, of Cambridge, Mass., a subsidiary of Takeda Pharmaceutical Co. Ltd., reported Phase I/II data showing that Velcade (bortezomib) produced hematologic overall response rates, as measured by serum and urine M-protein levels, of 69 percent in the weekly group and 67 percent in the twice-weekly group of patients with relapsed or refractory light chain amyloidosis. Complete response rates were 37 percent and 24 percent, respectively. More than 76 patients had a duration of response of one year or longer. In separate presentations, Millennium reported Phase I data establishing a dose of 1.76 mg/m2 for its next-generation proteasome inhibitor MLN9708; reported a recommended Phase II dose of 50 mg twice daily for its selective Aurora A kinase inhibitor, MLN8237, which demonstrated stable disease in 42 percent of solid tumor patients; presented Phase I/II data showing that selective 17,20 lyase inhibitor TAK-700 reduced prostate-specific antigen by 50 percent or greater in 52 percent of patients; and reported Phase I data showing no dose-limiting toxicities and dose-proportional pharmacokinetics for TAK-701, a humanized monoclonal antibody against HGF.
The National Cancer Center Singapore reported that a combination of liver-targeted radioactive microspheres (SIR-Spheres) and systemic agent Nexavar (sorafenib, Onyx Pharmaceuticals Inc. and Bayer Healthcare) appeared to confer a survival benefit for patients with inoperable primary hepatocellular cancer, including those with disease that has spread outside the liver. Data from the 35-patient, Phase II study showed a median overall survival of 11.75 months. Overall survival for patients with major vascular invasion and/or extra-hepatic spread vs. those without MVI/EHS was 8.75 months and 18.25 months, respectively. A previous Asia-Pacific Nexavar-only study had demonstrated an overall survival of 5.6 months and 14.3 months, respectively.
Nektar Therapeutics Inc., of San Carlos, Calif., reported positive Phase II data from a single-agent study of NKTR-102 in platinum-resistant/refractory ovarian cancer, which showed confirmed and unconfirmed response rates of 41 percent (14 of 34 patients) in the once-every-14-days dosing schedule and 41 percent (14/34) for the once-every-21-days dosing schedule. Confirmed response rates were 29 percent (10/34) and 38 percent (13/34) in the two dosing regimens, respectively. The trial enrolled 68 patients, half of whom were platinum refractory.
NewLink Genetics Corp., of Ames, Iowa, reported Phase II data showing that its HyperAcute-Pancreas cancer immunotherapy combined with standard adjuvant chemotherapy in patients with surgically resectable pancreatic cancer resulted in disease-free survival of 17 months and one-year overall survival of 96 percent. That compares to published studies of standard therapies that have showed median disease-free survival of about 11 months and one-year survival rates of about 70 percent. The immunotherapy also was well tolerated, with no serious adverse events. The trial enrolled 70 patients who received NewLink's vaccine plus gemcitabine and 5FU-based chemoradiation. The company recently began a 722-patient Phase III study. (See BioWorld Today, May 28, 2010.)
Novartis Pharmaceuticals Corp., of East Hanover, N.J., a subsidiary of Novartis AG, presented Phase II results showing that Afinitor (everolimus) decreased the size of subependymal giant cell astrocytomas, benign brain tumors associated with tuberous sclerosis. Data from the 28-patient trial showed that 21 subjects (75 percent) experienced a reduction of 30 percent or greater in the size of their brain tumors from baseline to six months.
OncoGenex Pharmaceuticals Inc., of Bothell, Wash., reported final results from a 36-patient Phase I trial of OGX-427, given at doses up to 1,000 mg to patients with various solid tumors, showing that the drug was safe and well tolerated as a monotherapy, as well as in combination with docetaxel. In addition, OGX-427 as a single agent demonstrated declines in circulating tumor cells at all doses and in all diseases evaluated, with nine of 26 evaluable patients showing CTCs of five tumor cells or less. Three of 17 evaluable patients receiving monotherapy treatment also had a decrease in measurable disease of 20 percent or greater. Two of four patients with ovarian cancer had a decrease of 25 percent or greater in CA-125 and three of 15 patients with prostate cancer had a decrease of 30 percent or greater in prostate-specific antigen. OGX-427 is designed to reduce levels of Hsp27.
Oncolytics Biotech Inc., of Calgary, Alberta, reported updated results from its Phase I/II UK trial of Reolysin combined with paclitaxel/carboplatin in patients with advanced cancers, showing that two of five patients with head and neck cancer had partial responses in the Phase I portion. Of the 19 head and neck cancer patients in the Phase II portion, eight (42 percent) had partial responses and six (32 percent) had stable disease. The mean overall survival in 24 treated head and neck cancer patients is more than eight months, with four patients currently still alive. One additional partial response and one stable disease were seen among four patients with malignant melanoma. Shares of Oncolytics (NASDAQ:ONCY) dropped 41 cents, or 13 percent, to close Monday at $2.74.
Oncothyreon Inc., of Seattle, said results from a Phase I trial of PX-866, an irreversible inhibitor of PI3 kinase showed that the drug was well tolerated in both the intermittent and continuous dosing arms, with no significant increase in adverse events noted in patients receiving more than two cycles of treatment in either arm of the trial. The maximum tolerated dose of PX-866 was 12 mg in the intermittent schedule and 8 mg in the continuous schedule. In the ongoing continuous dosing arm, six of eight patients evaluable to date had stable disease as the best response, while seven of 45 patients in the intermittent arm had stable disease. Oncothyreon also presented Phase I data for PX-478, an HIF-1-alpha inhibitor, showing that 13 of 37 evaluable patients (35 percent) had stable disease. Pharmacodynamic studies revealed dose-proportional inhibition of HIF-1-alpha levels.
Oxigene Inc., of South San Francisco, said updated data from its randomized, Phase II FALCON trial of Zybrestat in non-small-cell lung cancer showed improvements in response rate, progression-free survival and overall survival rates when the drug was combined with Avastin (bevacizumab, Genentech Inc./Roche AG) and carboplatin/paclitaxel chemotherapy compared to the control arm (Avastin and carboplatin/paclitaxel chemotherapy). The median PFS for the Zybrestat arm was 6.9 months vs. 6.2 months in the control arm, representing a 30 percent reduction in the odds of progression for patients on Zybrestat. The partial response rate was 60 percent in the Zybrestat arm compared to 40 percent in the control group. Median survival has not been reached in either arm. In a separate presentation, Oxigene and the UK's Mount Vernon Cancer Research Centre reported positive final data from a 45-patient Phase I study of OXi4503, showing partial responses in two patients with epithelial ovarian cancer and stable disease observed in nine patients. Shares of Oxigene (NASDAQ:OXGN) fell 19 cents, or 24.4 percent, to close Monday at 59 cents.
Pfizer Inc., of New York, reported Phase II data showing that bosutinib, an oral, dual Src and Bcr-Abl kinase inhibitor, in patients with Philadelphia chromosome-positive chronic phase chronic myeloid leukemia who are resistant or intolerant to Gleevec (imatinib, Novartis AG) produced a complete cytogenic response (CCyR) rate in 43 percent of 159 evaluable patients and a major cytogenic response (MCyR) in 56 percent. Of the 56 imatinib-intolerant patients evaluable, 70 percent achieved MCyR and 59 percent achieved a CCyR. In a separate presentation, Pfizer reported data from an expansion cohort from a Phase I/II study showing that nearly 60 percent of non-small-cell lung cancer patients with alterations of the ALK gene had either a complete or partial response to treatment with crizotinib (PF-02341066), an anaplastic lymphoma kinase inhibitor. Overall, the disease control rate was 87 percent at eight weeks.
Pharmacyclics Inc., of Sunnyvale, Calif., presented Phase I data showing that its oral, Bruton's tyrosine kinase inhibitor PCI-32765 in relapsed or refractory B-cell non-Hodgkin's lymphoma, has been well tolerated. Seventeen of 35 evaluable patients had a partial or complete response, representing an overall response rate of 49 percent - 82 percent of chronic lymphocytic leukemia patients, 75 percent in mantle-cell lymphoma, 27 percent in follicular lymphoma, 33 percent in marginal lymphoma and 17 percent in diffuse large B-cell lymphoma. The drug also appeared to be well tolerated, with two patients of the 47 enrolled experiencing a dose-limiting toxicity during the trial. Shares of Pharmacyclics (NASDAQ:PCYC) fell 86 cents, or 13 percent, to close Monday at $5.70.
Plexxikon Inc., of Berkeley, Calif., reported Phase I extension study results showing that PLX4032, an oral, small molecule targeting a BRAF mutation, resulted in one confirmed partial response in 19 evaluable metastatic colorectal cancer patients, four minor responses. Five of the 19 patients had mixed responses, with both regressing and progressing lesions. Data also showed a median progression-free survival of 3.7 months, with one patient still on study. PLX4032 is being co-developed by Roche AG, of Basel, Switzerland, and is in a Phase III trial in metastatic melanoma.
Poniard Pharmaceuticals Inc., of South San Francisco, said full efficacy and safety data from its Phase III SPEAR (Study of Picoplatin Efficacy After Relapse) trial in second-line non-small-cell lung cancer showed a statistically significant difference in favor of the picoplatin arm in progression-free survival in the intent-to-treat population, with a PFS of 9 weeks compared to 6.6 weeks in the standard-of-care arm and a median time to progression of 11.3 weeks vs. 6.7 weeks. As previously reported, the trial failed to hit its primary endpoint of overall survival, with median OS in the treatment arm of 20.6 weeks vs. 19.7 weeks in the standard-of-care arm, which Poniard has said could be attributed potentially to an imbalance in the use of post-study chemotherapy. Among the 273 patients who did not receive post-study chemotherapy, the picoplatin arm demonstrated a statistically significant improvement in OS, with a median survival of 18.3 weeks compared to 14.4 weeks for standard of care. (See BioWorld Today, Nov. 17, 2009.)
Rosetta Genomics Ltd., of Rehovot, Israel, said interim data from an ongoing prospective study in collaboration with the University of Texas M.D. Anderson Comprehensive Cancer Center showed that miRview mets, a microRNA-based diagnostic test, was able to identify the most likely origin of metastases origin in 84 percent (62 of 89) cases that were successfully processed.
Seattle Genetics Inc., of Bothell, Wash., and Millennium, of Cambridge, Mass., a subsidiary of Takeda Pharmaceutical Co. Ltd., reported preliminary data demonstrating objective responses in seven of 11 (64 percent) re-treatment experiences with brentuximab vedotin in Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, with the drug well tolerated in the re-treatment setting. Responses included two complete remissions and five partial remissions, with the time to objective response ranging from five weeks to 15 weeks. The duration of re-treatment objective responses ranged from less than one week to 58-plus weeks. Brentuximab vedotin is an antibody-drug conjugate comprising an anti-CD30 antibody and is in pivotal testing in relapsed and refractory Hodgkin lymphoma.
Sunesis Pharmaceuticals Inc., of South San Francisco, said updated Phase II data showed that voreloxin in combination with cytarabine in first relapsed or primary refractory acute myeloid leukemia exhibited a meaningful improvement in overall survival relative to literature-based values. Among 69 evaluable patients, the median overall survival is 7.1 months, with more than 80 percent either primary refractory or with an initial first remission of less than 12 months. Preliminary median leukemia-free survival is 10.8 months. Data from a 113-patient Phase II trial testing voreloxin as a single agent in newly diagnosed elderly AML demonstrated a median overall survival of 7.7 months and one-year survival of about 38 percent. Sunesis also presented Phase II ovarian cancer data showing that voreloxin, as a single agent, showed antitumor activity across all three dose cohorts in women with platinum-resistant disease. For cohort B, which tested 60 mg/m2 of voreloxin given every four weeks, 54 percent of patients achieved disease control, including an 11 percent objective response rate. Shares of Sunesis (NASDAQ:SNSS) fell 12.8 percent, or 10 cents, to close Monday at 68 cents.
Syndax Pharmaceuticals Inc., of Waltham, Mass., reported final results from the Phase II ENCORE trial of entinostat, a selective histone deacetylase inhibitor, in postmenopausal women with advanced, estrogen receptor-positive breast cancer who were progressing on aromatase inhibitor therapy. Data showed that, of the 26 evaluable patients, one achieved a partial response and three achieved stable disease of greater than six months. The total clinical benefit rate was 15.4 percent, exceeding the pre-specified rate of 5 percent defined in the study design, with a "p" value of 0.039. Secondary endpoints were objective response and progression-free survival, which were 3.9 percent and a median of 4.8 months, respectively.
Synta Pharmaceuticals Corp., of Lexington, Mass., reported data from two Phase I trials of STA-9090 in solid tumors, showing that the drug is well tolerated and has promising clinical efficacy, with no evidence of the severe hepatic or ocular toxicity observed with other Hsp90 inhibitors. The firm also presented 12-month, updated survival results from the SYMMETRY trial of elesclomol in metastatic melanoma, which demonstrate a differential response to treatment based on level of baseline lactate dehydrogenase. Elesclomol, an oxidative stress inducer, was placed on clinical hold following reports of an imbalance of deaths in the melanoma study, but the FDA approved resuming development earlier this year. Synta plans to start one or more studies of elesclomol in the second half of this year. (See BioWorld Today, March 2, 2009.)
Ziopharm Oncology Inc., of New York, presented updated data from PICASSO, a Phase II trial testing palifosfamide plus doxorubicin vs. doxorubicin alone on soft-tissue sarcoma patients, which previously met its endpoint of progression-free survival. Additional data showed a hazard ratio of 0.43 favoring the palifosfamide combination, with a statistically meaningful 3.4-month difference in median PFS. The response rate for the palifosfamide group was 23 percent (seven of 30 patients), while the doxorubicin-only arm had a response rate of 9 percent (three of 32 patients).