On February 4, 2015 OncoMed Pharmaceuticals reported that patient dosing has begun in the double-blinded, placebo-controlled, randomized Phase 2 clinical trial of demcizumab (anti-DLL4, OMP-21M18) for the treatment of patients with first-line advanced-stage non-small cell lung cancer (NSCLC) (Press release OncoMed, FEB 4, 2015, View Source [SID:1234501460]).
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"Based on anti-tumor activity and the safety profile observed in our Phase 1b study of demcizumab plus standard-of-care in non-small cell lung cancer, we believe demcizumab has the potential to achieve meaningful clinical benefits for patients with this difficult cancer. We look forward to assessing, with the study investigators, demcizumab’s activity and safety in a randomized setting," said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer.
The Phase 2 "DENALI" trial is expected to enroll approximately 200 patients with first-line metastatic Stage IV non-squamous NSCLC whose tumors do not have an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation. Patients will be randomized into one of three study arms to compare the efficacy and safety of demcizumab combined with carboplatin and pemetrexed versus carboplatin and pemetrexed alone. In all three arms, patients will receive carboplatin and pemetrexed for four cycles, followed by pemetrexed maintenance. In addition, patients in Arm 1 will receive the chemotherapy plus placebo, patients in Arm 2 will receive chemotherapy with one truncated course of demcizumab every three weeks for four doses and patients in Arm 3 will receive chemotherapy with two truncated courses of demcizumab with the second truncated course starting at Day 168. The primary endpoint is progression-free survival. Secondary endpoints include response rate, duration of response, overall survival, safety, immunogenicity and pharmacokinetics. The DENALI study will also explore pharmacodynamics and several potential predictive biomarkers. DENALI will be conducted at approximately 60 sites in Europe, the United States and Australia.
"This is a major milestone for us, as it is the first of two randomized Phase 2 trials being conducted for demcizumab in our collaboration with Celgene, and the first anti-DLL4 antibody to enter this phase of development. Patient dosing for the second demcizumab randomized Phase 2 trial in pancreatic cancer should also begin shortly. Two additional Phase 2 trials are already underway for tarextumab, our anti-Notch2/3 antibody. Depending on each study’s rate of enrollment and other factors, we expect these four randomized Phase 2 studies to produce results in the 2016-2017 timeframe," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer.
In OncoMed’s Phase 1b clinical study of demcizumab in NSCLC, the combination of demcizumab with pemetrexed and carboplatin was generally well tolerated. No moderate to severe cardiopulmonary adverse events occurred with truncated demcizumab administration. Of 33 patients evaluable for efficacy, one (3%) had a complete response, 15 (45%) had a partial response and 13 (39%) had stable disease per RECIST criteria for an overall clinical benefit rate of 88 percent. Among the 14 evaluable patients who received demcizumab on a truncated dosing schedule, one had a complete response, seven had a partial response, five achieved stable disease and one had progressive disease resulting in an overall clinical benefit rate in this subset of patients of 93 percent. Eight patients treated with demcizumab at or above the Phase 2 dose schedule had progression-free survival for greater than 300 days. Final clinical data from this Phase 1b trial are anticipated to be presented at a medical meeting in 2015.