Clinical Trials

Date: 2016-01-11

Type of information: Treatment of the first patient

phase: 1

Announcement: treatment of the first patient

Company: OncoMed Pharmaceuticals (USA - CA)

Product: rosmantuzumab - OMP-131R10 (anti-RSPO3 antibody)

Action mechanism: monoclonal antibody. R-spondin proteins bind to or activate leucine-rich repeat containing G-coupled receptors (LGRs) and blocking this activity has been shown to inhibit tumor growth. In preclinical studies OncoMed's anti-RSPO3 antibody demonstrated robust in vivo anti-tumor efficacy as a single agent and in combination with standard of care across a range of solid tumors, including colon, lung, ovarian, and pancreatic cancers, among others. The anti-RSPO3 antibody delayed tumor recurrence following termination of chemotherapy, and decreased the frequency of cancer stem cells. The anti-RSPO3 antibody represents the third drug in the clinic that is part of OncoMed's collaboration with Celgene.

Disease: advanced refractory solid tumors, metastatic colorectal cance

Therapeutic area: Cancer - Oncology

Country: USA

Trial details: This open-label Phase 1a/b dose-escalation study is assessing the safety, tolerability, and PK of OMP-131R10 as a single agent for advanced solid tumors and in subjects with metastatic colorectal cancer. (NCT02482441)

Latest news:

• • On November 29, 2016, OncoMed Pharmaceuticals presented initial first-in-human data from its ongoing Phase 1 clinical trial of anti-RSPO3 (OMP-131R10) antibody at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium being held in Munich, Germany. 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.
• • On January 11, 2016, OncoMed Pharmaceuticals  announced that the first patient has been enrolled and dosed in the Phase 1b portion of the Phase 1a/1b clinical trial of anti-RSPO3 (OMP-131R10). The Phase 1b portion of the trial will assess the safety, pharmacokinetics, pharmacodynamics and initial evidence of efficacy of anti-RSPO3 in combination with the chemotherapeutic standard of care in metastatic colon cancer, known as FOLFIRI (folinic acid, fluorouracil and irinotecan) in colorectal cancer patients who have received one prior treatment. The company's ongoing Phase 1a/1b clinical trial is initially enrolling patients with advanced refractory solid tumors to assess the safety, pharmacokinetics, pharmacodynamics and initial evidence of efficacy of the anti-RSPO3 antibody. Enrollment commenced on the single-agent portion of the anti-RSPO3 first-in-human clinical trial in July 2015. Now that several dose cohorts have been safely cleared the decision has been made by OncoMed and the investigators of the trial to initiate the combination phase of the study. Dose escalation of the single agent portion of the study continues in parallel. Once a single-agent dose has been identified, biomarker-selected patients will be enrolled in a Phase 1a expansion arm to evaluate possible anti-tumor activity.
• • On July 28, 2015, OncoMed Pharmaceuticals announced dosing of the first patient in its anti-RSPO3 antibody (OMP-131R10) Phase 1a/1b clinical trial. Anti-RSPO3 is the first drug in its class to target the R-spondin-LGR pathway, an important cancer stem cell pathway identified by OncoMed researchers. The Phase 1a/1b clinical trial is initially enrolling patients with advanced refractory solid tumors. Patients will receive escalating doses of anti-RSPO3 until disease progression. The open-label study is designed to assess the safety, pharmacokinetics, pharmacodynamics and initial evidence of efficacy of the anti-RSPO3 antibody. Once a single-agent dose has been identified, biomarker-selected patients will be enrolled in a Phase 1a expansion arm to obtain additional preliminary information on possible anti-tumor activity. In the Phase 1b portion of the trial, anti-RSPO3 will also be tested in second-line colorectal cancer patients in combination with the chemotherapeutic standard of care in metastatic colon cancer, known as FOLFIRI (folinic acid, fluorouracil and irinotecan). The trial is being conducted at five sites in the United States.

Is general: Yes