Partial Responses and Stable Disease Achieved with Bispecific as a Single-Agent
Safety and Target Engagement Established for Anti-RSPO3
REDWOOD CITY, Calif., Nov. 29, 2016 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) presented initial first-in-human data from its ongoing Phase 1 clinical trials of anti-DLL4/VEGF bispecific (OMP-305B83) and anti-RSPO3 (OMP-131R10) antibodies in two posters at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium being held in Munich, Germany.
“In these first-in-human Phase 1 trials of our anti-DLL4/VEGF bispecific and anti-RSPO3 antibodies we have accomplished the primary goal of defining the safety profiles and establishing the single-agent doses for these agents. We have also observed initial evidence of anti-tumor activity in patients treated to date,” said Jakob Dupont, M.D., Chief Medical Officer of OncoMed. “Dual blockade of DLL4 and VEGF has shown synergies preclinically, and in the clinic we are seeing evidence of single-agent activity with partial responses in ovarian and uterine cancers and stable disease in about one-third of the Phase 1 patients treated. We look forward to completing these trials and, in the near future, initiating Phase 1b studies with the anti-DLL4/VEGF bispecific in combination with standard of care in ovarian and colorectal cancers.”
Dr. Dupont continued, “Data from the ongoing anti-RSPO3 Phase 1a/b trial show evidence of target engagement and some encouraging signals of prolonged stable disease. With a single-agent dose identified and a good understanding of the safety profile of anti-RSPO3, we are excited to continue enrolling the biomarker-selected and combination portions of this study. Overexpression of RSPO3 is associated with the growth of a number of solid tumors, including colorectal cancers, and we have developed a CLIA-validated assay and a custom liquid biopsy to identify tumors with RSPO3 high gene expression and gene fusions where responses to treatment may be more likely.”
Anti-DLL4/VEGF Bispecific – Interim Phase 1a Data in Advanced Solid Tumors
As of the data cut off of October 17, 2016, a total of 51 patients with advanced solid tumors had received single-agent doses ranging from 0.5 to 12.5 mg/kg every three weeks in the ongoing Phase 1a clinical trial of OncoMed’s anti-DLL4/VEGF bispecific antibody.
Safety and Pharmacokinetics: Anti-DLL4/VEGF bispecific was generally well tolerated with hypertension, headache, fatigue and pulmonary hypertension being the most common drug-related toxicities. One dose-limiting toxicity of diverticulitis occurred at 2.5 mg/kg. Hypertension side effects were successfully managed with anti-hypertensives and most pulmonary hypertension adverse events were reversible and of mild to moderate severity. A dose of 7.5 mg/kg once every three weeks was set for the Phase 1a expansion cohort following the observation of Grade 3 and 4 toxicities at the 10 mg/kg dose. The anti-DLL4/VEGF bispecific had a half-life of 14 days and anti-drug antibody response occurred primarily at low doses (=3.5 mg/kg).
Efficacy: Two of the 46 patients (4%) evaluable for anti-tumor effects had unconfirmed partial responses, while another sixteen (35%) patients achieved stable disease. The partial responses occurred in patients with ovarian cancer and uterine carcinosarcoma. Five of eight evaluable ovarian patients had reductions in tumor volume and remained on therapy for 129, 170, 185, 309 and 323 days as of the data cut off.
Data from the ongoing Phase 1a trial of the anti-DLL4/VEGF bispecific were presented in a poster titled, “A first-in-man Phase 1a study of the bispecific anti-DLL4/anti-VEGF antibody OMP-305B83 in patients with previously treated solid tumors “(Poster #P057; Abstract #87) by Dr. Kathleen Moore of the Stephenson Oklahoma Cancer Center at the University of Oklahoma.
Anti-RSPO3 – Interim Phase 1a/b Data in Advanced Solid Tumors and Colorectal Cancer
As of the data cut-off date of October 11, 2016, 23 patients in the anti-RSPO3 Phase 1a/b clinical trial were evaluable for safety and 15 patients were evaluable for anti-tumor activity. Interim safety, response, pharmacokinetics and biomarker data were included in the analyses in this ongoing clinical trial.
Safety and Pharmacokinetics: Anti-RSPO3 was generally well tolerated as a single agent with the most common adverse events being fatigue and nausea in sixteen subjects treated at doses ranging from 2.5 to 15 mg/kg every two weeks. No dose-limiting toxicities were observed. Based on evidence of target engagement observed by changes in serum biomarkers, a single-agent dose of 15.0 mg/kg every two weeks was selected. Anti-RSPO3 has an estimated half-life of 13 days.
Among seven safety-evaluable Phase 1b colorectal cancer patients who received anti-RSPO3 in combination with FOLFIRI (folinic acid, fluorouracil and irinotecan) chemotherapy the combination did not appear to exacerbate the toxicities of either drug. Dose-escalation continues in the combination portion of the trial.
Efficacy and Biomarkers: In the single-agent Phase 1a portion of the trial, five of eleven patients achieved stable disease and three of those five patients were RSPO3 high, with RSPO3 levels in a fourth patient slightly below the current cut point of OncoMed’s CLIA-validated biomarker assay. Three of the stable disease patients in the Phase 1a portion of the trial demonstrated prolonged stable disease of greater than 112 days as of the data cut off.
In the Phase 1b portion of the trial, three of four evaluable subjects who received the combination of anti-RSPO3 and FOLFIRI achieved stable disease.
Data from the anti-RSPO3 Phase 1a/b were presented in a poster titled: “Initial results from a Phase 1a/b study of OMP-131R10, a first-in-class anti-RSPO3 antibody, in advanced solid tumors and previously treated metastatic colorectal cancer (CRC)” (Poster #P039; Abstract #68) by Dr. Pamela Munster of the University of California, San Francisco.
Both posters from the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium are available on OncoMed’s website at www.oncomed.com.
The anti-DLL4/VEGF bispecific antibody (OMP-305B83) is designed to combine the anti-cancer stem cell, dysangiogenesis and immunotherapy mechanisms of anti-DLL4 with the anti-angiogenic activity of an anti-VEGF agent. It was developed utilizing OncoMed’s BiMAb™ bispecific platform technology, which enables the design of bispecific antibodies comparable to traditional monoclonal antibodies but possessing dual target-binding specificity. OncoMed initiated the single-agent study of its anti-DLL4/VEGF bispecific in January 2015 in patients with advanced refractory solid tumors. Dose escalation is complete in the Phase 1a trial and enrollment in an expansion cohort is ongoing. The bispecific antibody is part of OncoMed’s collaboration with Celgene.
Anti-RSPO3 (OMP-131R10) is believed to be the first drug candidate in its class to target the R-spondin-LGR pathway, an important cancer stem cell pathway identified by OncoMed researchers. OncoMed is currently enrolling patients in an ongoing Phase 1a/b clinical trial of anti-RSPO3 that was started in July 2015. The Phase 1a/b trial initially enrolled patients with advanced refractory solid tumors and includes an expansion arm for biomarker-selected patients to receive single-agent therapy. The Phase 1b portion, which began enrollment in January 2016, is testing anti-RSPO3 with FOLFIRI in patients with second-line metastatic colorectal cancer. Anti-RSPO3 is part of OncoMed’s collaboration with Celgene.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics. OncoMed has internally discovered a broad pipeline of investigational drugs intended to address the fundamental biology driving cancer’s growth, recurrence and metastases. Demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), anti-RSPO3 (OMP-131R10) and an undisclosed immuno-oncology candidate (I/O#2) are part of the company’s strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). OncoMed is independently developing brontictuzumab (anti-Notch1, OMP-52M51) and GITRL-Fc, as well as continuing to pursue new drug discovery research efforts. For further information about OncoMed Pharmaceuticals, please see www.oncomed.com.
To the extent that statements contained in this press release are not descriptions of historical facts regarding OncoMed Pharmaceuticals, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including OncoMed's expectations regarding the single-agent, anti-tumor activity of OncoMed’s anti-DLL4/VEGF bispecific antibody, particularly against ovarian and uterine cancers; the synergistic effect of dual blockade of DLL4 and VEGF; the ability of OncoMed to continue to enroll its anti-RSPO3 Phase1a/b trial and initiate Phase 1b clinical trials of its anti-DLL4/VEGF bispecific antibody; the timing of initiation of the Phase 1b studies of OncoMed’s anti-DLL4/VEGF bispecific antibody; the safety profile of anti-RSPO3; and the ability of OncoMed’s CLIA-validated assay and custom liquid biopsy to identify tumors where responses to treatment with anti-RSPO3 may be more likely. Such forward-looking statements involve substantial risks and uncertainties that could cause OncoMed's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the preclinical and clinical development process; OncoMed's dependence on its collaboration partners, including Celgene, GSK and Bayer, for the funding of its partnered programs; OncoMed's ability to raise additional capital to support the development of its unpartnered programs; OncoMed's reliance on third parties to conduct certain preclinical studies and all of its clinical trials; OncoMed's reliance on single source third-party contract manufacturing organizations to manufacture and supply its product candidates; OncoMed's ability to discover, develop and commercialize additional product candidates; and OncoMed's dependence on its key executives. OncoMed undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to OncoMed's business in general, see OncoMed's Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on March 10, 2016, OncoMed's Quarterly Report on Form 10-Q filed with the SEC on November 1, 2016, and OncoMed's other periodic reports filed with the SEC.