|
ASCO Roundup
(BioWorld Today Via Acquire Media NewsEdge) American Society of Clinical Oncology
Revlimid, Velcade Combo Shows Promise in First-Line MyelomaFrom Staff Reports
Among the data emerging at this year's American Society of Clinical Oncology meeting in Chicago were results showing that a combination treatment regimen of Celgene Corp.'s Revlimid (lenalidomide) and Millennium Pharmaceuticals' Velcade (bortezomib), along with dexamethasone, yielded a complete response rate of 35 percent and an overall response rate of 100 percent in newly diagnosed myeloma patients.
Those data, based on 66 evaluable patients in a Phase I/II study, were observed at the maximum planned dose of 1.3 mg/m2 Velcade, 25 mg Revlimid and 20 mg dexamethasone, and results were assessed using EBMT criteria and International Myeloma Working Group criteria. While both drugs continue to show strong myeloma data on their own, "combination or sequential Velcade/Revlimid use demonstrates the best quality responses seen to date," analysts from New York-based Cowen and Co. reported in a research note.
In other presentations, Cambridge, Mass.-based Millennium (now part of Osaka, Japan-based Takeda Pharmaceutical Co. Ltd.) showed that Velcade demonstrated a complete response rate of 46 percent prior to transplant and 72 percent post-transplant when administered in combination with cyclophosphamide and dexamethasone to newly diagnosed multiple myeloma patients.
The overall response rate was 95 percent. And when given in combination with Doxil (doxorubicin) and dexamethasone, Velcade showed a complete response rate of 21 percent in myeloma patients prior to transplant. That rate increased to 59 percent after transplant.
Summit, N.J.-based Celgene's Revlimid also yielded positive data in newly diagnosed patients. In combination with dexamethasone, the drug demonstrated a survival advantage and improved complete response rates, particularly with a low dose of dexamethasone. Patients receiving Revlimid plus low-dose dexamethasone demonstrated a combined near complete/very good partial response rate of 52 percent compared to 42 percent of patients getting Revlimid plus a standard dose of dexamethasone. Two-year survival was 88 percent for the Revlimid/low-dose dexamethasone arm vs. 78 percent in the Revlimid/standard-dose dexamethasone arm.
Data from a study of 255 patients who continued therapy after four cycles of treatment showed a two-year survival rate of 93 percent for those receiving Revlimid plus low-dose dexamethasone. Those results were identical for patients in the same arm who proceeded to stem cell transplant. Analyst Howard Liang, of Leerink Swann & Co. wrote in a research note that, while it's too early to conclude that patients should skip the stem cell transplant, those data "help to establish that continued treatment of Revlimid is associated with durable response and favorable overall survival."
Celgene also reported data from a study in non-Hodgkin's lymphoma, which showed that Revlimid achieved an objective response in 29 percent of patients, with 6 percent achieving a complete response, 23 percent a partial response and 19 percent showing stable disease.
Shares of Celgene (NASDAQ:CELG) closed at $61.20 Monday, up 34 cents.
In other ASCO news (see also pp. 9-12):
? Abraxis BioScience Inc., of Los Angeles, reported results from an ongoing Phase II trial evaluating solvent-free Abraxane in combination with trastuzumab (Herceptin, Genentech Inc.) and carboplatin in first-line treatment of patients with HER2-positive metastatic breast cancer. Preliminary analysis showed that weekly Abraxane, followed by carboplatin plus trastuzumab, demonstrated a 53 percent overall response rate and median progression-free survival of nearly 16 months.
? Adherex Technologies Inc., of Research Triangle Park, N.C., reported updated results from its ongoing Phase I/II study of ADH-1, a peptide designed to target N-cadherin-mediated cell adhesion, in combination with isolated limb infusion melphalan for the treatment of melanoma. Of 20 patients who have completed three months of follow-up, 10 have experienced in-field complete response.
? Amgen Inc., of Thousand Oaks, Calif., reported Phase II data showing that 71 percent of denosumab-treated patients achieved the primary endpoint of urinary N-telopeptide levels less than 50 at week 13, and that the drug also induced suppression of uNTx levels faster than I.V. bisphosphonate in metastatic cancer patients. Data from additional Phase II studies showed that denosumab produced consistent reduction of bone resorption in either bisphosphonate-naive or -treated patients, and subgroup analysis of a Phase III trial showed that the drug increased bone mineral density throughout the skeleton in women with non-metastatic breast cancer receiving aromatase inhibitor treatment. Data from another Phase II study demonstrated that 13 of 15 patients had tumor response to denosumab treatment. Other data included results from a Phase Ib trial of rhApo2L/TRAIL, a pro-apoptotic receptor agonist, which showed a best overall objective tumor response, per RECIST criteria, of 58 percent in combination with a regimen of paclitaxel, carboplatin and bevacizumab.
? Antisense Pharma GmbH, of Regensburg, Germany, reported a two-year survival rate of more than 80 percent in patients with recurrent or refractory anaplastic astrocytoma in a Phase III trial of AP 12009. Efficacy results showed that the 10 mg dose of AP 12009 is superior to standard chemotherapy, with a current median survival time of 37.2 months vs. 21.7 months in the control arm. The company also reported data from a separate study showing that AP 12009 achieved a median survival time of 29.6 weeks after start of treatment in patients with Stage IV pancreatic carcinoma.
? Antisoma plc, of London, presented data on its tumor vascular disrupting agent ASA404, which is licensed to Basel, Switzerland-based Novartis AG., in lung and colon cancer. Non-small-cell lung cancer patients receiving ASA404 with carboplatin and paclitaxel in a Phase II trial showed a 3.9 month to 4.7 month increase in median overall survival rate depending on the subgroup. In a separate trial, prostate cancer patients receiving the drug showed increased prostate-specific antigen and tumor response rates.
? Apthera Inc., of Scottsdale, Ariz., reported that analysis of five-year follow-up data from a Phase I/II trial on its NeuVax (E75) showed that the HER2/neu-targeted peptide-based T-cell immunotherapy produced a delay in disease recurrence in high-risk, disease-free, HER2-positive prostate cancer patients.
? ArQule Inc., of Woburn, Mass., said a Phase I trial of ARQ 197 demonstrated that the compound is safe and well tolerated at oral doses up to 300 mg twice daily, with dose-limiting toxicity observed at 400 mg twice daily. Analysis of tumor biopsy samples from patients in the trial who received from 100 mg to 300 mg of ARQ 197 twice daily confirmed the inhibition of c-Met by ARQ 197.
? Barbara Ann Karmanos Cancer Institute, of Detroit, said researchers presented findings that showed immunotherapy with armed targeted T cells may improve the overall survival of women with metastatic breast cancer.
? BioVex Inc., of Woburn, Mass., reported positive results from its Phase II trial of OncoVEX GM-CSF, an oncolytic for the treatment of advanced metastatic melanoma. Among 43 patients of the 50 patients enrolled, tumors injected with OncoVEX GM-CSF routinely responded, often with local complete responses or palliative benefit. Six patients showed complete clinical responses, five of which are ongoing at four to 27 months after the first injection.
? BiPar Sciences Inc., of Brisbane, California., said its lead product, BSI-201, demonstrated safety and clinical benefit as a monotherapy and combination therapy in Phase I/Ib trials. In addition, significant and prolonged PARP inhibition in blood cells was observed after multiple doses of BSI-201.
? Cell Genesys Inc., of South San Francisco, presented interim data from the ongoing Phase I trial of GVAX immunotherapy in combination with ipilimumab (Medarex Inc.) in patients with advanced prostate cancer. Of the 12 patients enrolled in the escalation cohort, antitumor activity was observed in five of the six patients who received the two highest doses of ipilimumab, including prostate-specific antigen declines of greater than 50 percent.
? Cell Therapeutics Inc., of Seattle, said two studies suggested that Zevalin (ibritumomab tiuxetan) radioimmunotherapy might be useful in stem cell transplantation for non-Hodgkin's lymphoma. The company markets Zevalin in the U.S.
? CuraGen Corp., of Branford, Conn., presented results from an ongoing Phase I/II study of CR011-vcMMAE in unresectable Stage III or Stage IV melanoma. Based on observation of dose-dependent objective responses, tumor shrinkage and encouraging early progression-free rate at 12 weeks, the company is exploring additional dosing schedules and plans to expand its program to include a Phase II trial in metastatic breast cancer.
? Curis Inc., of Cambridge, Mass., said it presented data from a Phase I study of GDC-0449 in patients with advanced solid tumors. Partial responses were achieved in two patients with advanced basal-cell carcinoma, and stable disease was achieved in two patients with adenocystic carcinoma, a rare cancer most commonly found in the salivary glands.
? EntreMed Inc., of Rockville, Md., said preclinical data for its Aurora A/angiogenesis kinase inhibitor, ENMD-981693, demonstrated antitumor activity in a multiple myeloma model. ENMD-2076 free base exhibited dose-dependent cytotoxicity toward multiple myeloma cell lines and was shown to induce cell death in vitro following relatively short (six hour) exposures through apoptosis via a mitochondrial pathway.
? Exelixis Inc., of South San Francisco, reported interim data from a Phase I dose-escalation trial of XL765, which indicated that XL765 inhibits the PI3K/mTOR pathway in patients at well-tolerated doses. In addition, the company reported data from an ongoing Phase I trial of XL184, in patients with advanced malignancies, with results showing that, across all tumor types, 10 of 60 patients had partial responses as determined by RECIST criteria. The company also reported data from three clinical trials of XL647, a novel small-molecule inhibitor of EGFR, HER2 and VEGFR2, including results showing encouraging antitumor activity of XL647 administered on an intermittent dosing schedule or a continuous daily dosing schedule.
? Fresenius Biotech GmbH, of Bad Homburg, Germany, and Trion Pharma GmbH, of Munich, Germany, reported that treatment with catumaxomab significantly prolonged puncture-free survival in patients with malignant ascites in a Phase II/III trial. Patients treated with catumaxomab showed a median puncture-free survival of 46 days compared to 11 days in the control group.
? Genentech Inc., of South San Francisco, said Avastin (bevacizumab), in combination with docetaxel, significantly increased the time women with metastatic breast cancer receiving first-line therapy lived without their disease advancing. Data from the AVADO trial showed that Avastin plus docetaxel improved progression-free survival by up to 64 percent in the 15 mg/kg treatment arm and by up to 45 percent in the 7.5 mg/kg arm compared to chemotherapy alone.
? Genta Inc., of Berkeley Heights, N.J., released final results from its Phase I trial of G4544, showing that the drug was well tolerated, and that blood levels were achieved in a range that is known to be clinically bioactive.
? GenVec Inc., of Gaithersburg, Md., said results from a Phase I trial of TNFerade in patients with head and neck cancer showed that nine of 10 evaluable patients in the trial achieved an objective response to treatment. Of those patients, four achieved complete clinical response by RECIST criteria.
? Genzyme Corp., of Cambridge, Mass., said that preliminary data from a fully enrolled pivotal Phase II study, known as CLASSIC-II, examining the safety and effectiveness of Clolar (clofarabine) as a single agent in previously untreated, older adult patients with acute myelogenous leukemia showed that patients with unfavorable prognostic factors exhibited a 45 percent overall remission rate based on investigator assessment, with manageable treatment-related side effects. The 30 day all-cause mortality, one of the secondary endpoints in the study, was only 9.6 percent, which it said compares favorably with existing treatment options.
? Geron Corp., of Menlo Park, Calif., said data from trials of GRN163L demonstrated selective cytotoxicity on T-PLL cells, which led to rapid leukemic cell death. In addition, an interim analysis of an ongoing Phase I study of GRN163L in refractory, advanced solid tumor patients showed a plasma half-life of about three hours. Dose-limiting toxicity was observed in one patient at the 3.2 mg/kg dose and in two patients out of 14 at the 4.8 mg/kg dose. No objective responses have been seen at those dose levels.
? GPC Biotech AG, of Martinsried, Germany, reported overall survival results from the Phase III satraplatin trial, with median survival of 61.3 weeks for the satraplatin arm vs. 61.4 weeks for the control group. The 950-patient trial missed its endpoint, but when adjusted for certain prognostic factors, showed a positive trend in those patients who had progressed after receiving docetaxel. GPC also presented data from several Phase I trials, including results showing that satraplatin plus docetaxel had encouraging activity in men with high-grade androgen-independent prostate cancer.
? IDM Pharma Inc., of Irvine, Calif., reported follow-up results from a Phase II trial of IDM-2101 showing that it induced broadly specific cytotoxic T-lymphocyte responses and showed a positive survival trend in HLA-A2-positive patients with non-small-cell lung cancer compared to a parallel external control group of HLA-A2-negative nontreated patients. One-year survival in IDM-2101-treated patients was 60 percent vs. 49 percent in HLA-A2-negative patients. The company also reported an analysis from its Phase III study of mifamurtide, which suggested that the addition of the drug to chemotherapy improved overall survival, with a 25 percent reduction in the risk of death in newly diagnosed metastatic osteosarcoma patients.
? Immunogen Inc., of Waltham, Mass, reported clinical findings with its targeted cancer compounds IMGN242 and AVE1642. Among the highlights were a substantial and sustained biological effect of AVE1642 when used in combination with docetaxel in the treatment of solid tumors and a marked biological response in one of six patients treated with IMGN242 in a Phase II study for gastric cancers.
? Infinity Pharmaceuticals Inc., of Cambridge, Mass., reported positive results from a Phase I trial of IPI-504 in metastatic and/or unresectable gastrointestinal stromal tumors (GIST) refractory to tyrosine kinase inhibitors. Results showed that patients with GIST, who were heavily pretreated, experienced a 70 percent overall disease control rate, with 3 percent partial response and 67 percent stable disease at six weeks. Estimated median progression-free survival for those patients was 12 weeks.
? Isis Pharmaceuticals Inc., of Carlsbad, Calif., said partner Indianapolis-based Eli Lilly and Co. presented data showing that LY2181308 was distributed to tumor cells with evidence of reduced survivin protein levels in tumor cells.
? Medarex Inc., of Princeton, N.J., presented Phase I and Phase II data showing that ipilimumab plus chemotherapy led to a median overall survival of 15 months in patients with advanced melanoma. The company also presented preliminary data from an ongoing Phase 1 trial of its investigational Anti-PD-1 antibody, MDX-1106, showing early evidence of antitumor activity.
? Medivation Inc., of San Francisco, said data from an ongoing Phase I/II trial of androgen receptor antagonist MDV3100 showed encouraging antitumor activity as measured by declining serum levels of prostate-specific antigen and circulating tumor cells, as well as radiographic disease stabilization after three months of treatment. To date, 90 patients have been enrolled in the trial with enrollment completed at doses up to 240 mg/day. The firm said MDV3100 has been well tolerated and dose escalation at 360 mg/day is in progress.
? Methylgene Inc., of Montreal, said preliminary data from two studies of its HDAC inhibitor, MGCD0103, demonstrated the compound's safety and clinical activity in a Phase I study in relapsed or refractory Hodgkin's lymphoma patients. Data for the 110-mg cohort showed eight patients with objective responses, or a 35 percent objective response rate for the overall cohort.
? Molecular Insight Pharmaceuticals Inc., of Cambridge, Mass., reported positive preliminary results from an ongoing Phase 1 study of Azedra in malignant pheochromocytoma, a type of neuroendocrine cancer. The study is the first segment of a Phase I/II study designed to assess safety and identify Azedra's maximum tolerated dose.
? Nektar Therapeutics Inc., of San Carlos, Calif., said data from a Phase I study of NKTR-102 (PEG-irinotecan) in advanced cancer patients whose tumors had progressed on other therapies showed significant antitumor activity at all dose schedules, with partial responses observed in seven of 44 total patients (16 percent). Repeat evidence of antitumor activity was observed in a number of tumor settings, including breast and ovarian.
? Novelos Therapeutics Inc., of Newton, Mass, said results from a Phase II trial of NOV-002 in platinum-resistant ovarian cancer patients showed that a combination of NOV-002 and carboplatin slowed disease progression in more than half of the 15 patients tested.
? Oncogenex Technologies Inc., of Vancouver, British Columbia, reported a better-than-expected 12.1 month median survival rate in a Phase II trial of 42 patients with hormone-refractory prostate cancer receiving its antisense oligonucleotide OGX-011 plus chemotherapy. The company also reported that low serum clusterin levels predicted survival.
? Oncolytics Biotech Inc., of Calgary, Alberta, reported interim Phase II results showing that treatment with intravenous Reolysin has been well tolerated to date and that eight of 16 evaluable patients with sarcomas metastatic to the lung experienced stable disease for periods ranging from two to more than 10 28-day cycles.
? Oncothyreon Inc., of Bellevue, Wash., reported results from a Phase I/II study designed to evaluate the safety of its investigational therapeutic cancer vaccine Stimuvax following a change in the manufacturer of the adjuvant component of the vaccine. No safety concerns were identified, and results from the study are in line with previous Phase II studies. Stimuvax currently is in Phase III trials for unresectable non-small-cell lung cancer.
? Onyx Pharmaceuticals Inc., of Emeryville, Calif., said data from Phase II trials of Nexavar (sorafenib) tablets in multiple tumor types including lung cancer showed that patients who remained on Nexavar had a longer period of disease control and stabilization than those who discontinued the drug.
? Oxford BioMedica plc, of Oxford, UK, and Sanofi-Aventis, of Paris, reported updated results from Phase II trials of TroVax in metastatic renal cancer, showing that the product was well tolerated and generated consistent and robust immune responses to the tumor antigen 5T4 in 55 of 60 evaluable patients.
? Peregrine Pharmaceuticals Inc., of Tustin, Calif., presented Phase II data from an ongoing trial evaluating bavituximab plus docetaxel in advanced breast cancer. Of 11 evaluable patients to date, none have experienced any measurable tumor growth or disease progression, with five of the 11 evaluable patients achieving a partial tumor response. The company also presented data from Phase I trials of bavituximab in combination with chemotherapy in patients with advanced cancer, and data from its Cotara in glioblastoma multiforme.
? Poniard Pharmaceuticals Inc., of South San Francisco, reported positive results from a Phase II trial in metastatic colorectal cancer patients, showing that picoplatin given in combination with 5-fluorouracil and leucovorin (FOLPI) might have similar antitumor activity to oxaliplatin given in combination with 5-fluorouracil and leucovorin (FOLFOX). Of 11 evaluable patients in the FOLPI arm, 10 achieved disease control, including partial responses; and of 13 evaluable patients in the FOLFOX arm, 10 achieved disease control, including one partial response. Data from a separate Phase II trial showed that picoplatin in combination with docetaxel and prednisone resulted in a prostate-specific antigen response rate of 69 percent in 26 first-line metastatic hormone-refractory prostate cancer patients.
? Reata Pharmaceuticals Inc., of Irving, Texas, said RTA 402 in patients with advanced cancers was shown to be safe and to provide a clinical benefit in a significant percentage of patients in a Phase I study. Investigators also confirmed that the drug was active against its biological targets, NF-kappa B and STAT3.
? Sunesis Pharmaceuticals Inc., of South San Francisco, said interim data from its ongoing Phase II trial in platinum-resistant ovarian cancer patients showed that voreloxin demonstrated clinical activity when administered as a single dose once over 21 days. Of the 62 evaluable patients, one had a complete response, five showed partial responses and 45 achieved stable disease.
? TransMolecular Inc., of Cambridge, Mass., said interim data from a Phase I study showed that intravenous radiolabeled TM601 in metastatic melanoma was able to cross the blood-brain barrier, specifically bind to tumor tissue and was actively internalized by tumor cells, including metastases to the central nervous system. Trial results revealed that all six of the evaluable patients with metastatic melanoma demonstrated tumor-specific uptake of radiolabeled TM601 based on the whole body planar gamma camera imaging.
? Vion Pharmaceuticals Inc., of New Haven, Conn., said interim data from the pivotal Phase II trial of its lead anticancer agent Cloretazine (VNP40101M) in elderly patients with de novo poor-risk acute myelogenous leukemia showed an overall complete response rate of 35 percent. About 90 percent of responses occurred after first induction treatment. The median overall survival for responders to date was 6.3 months and was 3.2 months for all patients. The induction death rate within 30 days of first induction treatment was 14 percent.
? VioQuest Pharmaceuticals Inc., of Basking Ridge, N.J., said a Phase I study of Lenocta in combination with IFN alpha-2b was well tolerated at 900 mg/m2 in the regimen studied. Thirteen patients who received Lenocta at 900 mg/m2 or higher demonstrated increased adaptive and innate immune responses, as evidenced by increased dendritic cells and CD4+ T-cells.
? Xanthus Pharmaceuticals Inc., of Cambridge, Mass., said results from the company's completed Phase II study of Xanafide in combination with cytarabine (ara-C) in secondary acute myeloid leukemia confirmed the preliminary complete remission rate results reported in June 2007. Similar complete remission rates were observed in the overall population, as well as in poor-risk subsets of secondary AML, including older patients, patients with treatment-related AML and patients who previously received treatment for their prior myelodysplastic syndrome.
? Xencor Inc., of Monrovia, Calif., said data from preclinical studies evaluating XmAb 5574, an Fc engineered monoclonal antibody targeting the antigen CD19, showed that it elicited complete B-cell depletion compared to undetectable B-cell depletion seen with an equal dose of a non-Fc engineered anti-CD19 1gG1 analogue. Additionally, the pharmacokinetics of XmAb5574 were shown to be indistinguishable from those of the 1gG1 analogue.
? YM BioSciences Inc., of Mississauga, Ontario, said it updated preliminary trial results, including survival, from its Phase I trial of nimotuzumab. The median survival was 60 weeks in patients with Stage IIb, III or IV non-small-cell lung cancer who are ineligible for chemotherapy-containing regimens.
?
?
Copyright ? 2008 Thomson BioWorld, All Rights Reserved.
[ Back To TMCnet.com's Homepage ]
|
INDUSTRIES
Activate Email 
INDUSTRIES
Find Solutions for Enterprises, SMBs & Service Providers at the INTERNET TELEPHONY Conference and EXPO West, September 1-3, 2009. Los Angeles, CA.
