OncoMed’s phase 2 trial of tarextumab in small cell lung cancer does not meet endpoints.
OncoMed Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, on Monday reported top-line results from the company’s randomized 145-patient phase 2 PINNACLE clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in combination with etoposide plus either cisplatin or carboplatin chemotherapy in previously untreated patients with extensive-stage small cell lung cancer.
Results for the combination of tarextumab plus chemotherapy were undifferentiated from those of chemotherapy plus placebo, and therefore the trial did not meet its primary endpoint of progression-free survival or secondary endpoints of overall survival and biomarkers reflective of Notch pathway gene activation.
“Small cell lung cancer is a very difficult-to-treat disease and unfortunately, tarextumab did not show benefit over placebo in this phase 2 trial,” said Paul J. Hastings, OncoMed’s Chairman and CEO. “We deeply appreciate the participation by the investigators and staff, patients and caregivers who all contributed to the conduct and completion of this phase 2 clinical trial.”
OncoMed also announced that it will discontinue enrollment in the phase 1b clinical trial of brontictuzumab (anti-Notch1, OMP-52M51) in combination with trifluridine/tipiracil (Lonsurf) in third-line colorectal cancer patients. The combination of brontictuzumab plus chemotherapy was not tolerable in this patient population.
“Based on the events of today and last week, we will be undertaking a comprehensive portfolio prioritization review immediately,” continued Mr. Hastings. “The immediate task ahead is to thoroughly examine the available data, our resources and the opportunities to re-focus our efforts. We ended the first quarter of 2017 with $156.9 million in cash and short-term investments.”
The median progression-free survival (mPFS) for tarextumab plus chemotherapy was 5.6 months versus 5.5 months for chemotherapy plus placebo (HR=0.969). The median overall survival (mOS) analysis did not show a benefit for tarextumab in combination with chemotherapy (mOS=9.3 months) compared to the chemotherapy plus placebo arm (10.3 months; HR=1.01).
Five individual Notch biomarkers (Hes1, Hes6, Hey1, Hey2 and Notch3) failed to identify a definitive subset of patients with a treatment effect on either mPFS or mOS. Overall response rates were 68.5% and 70.8% in the tarextumab and placebo arms respectively. The combination of tarextumab plus chemotherapy was well tolerated.
The safety profile appeared to be similar between the two groups except for diarrhea and thrombocytopenia, which were more prevalent in the tarextumab treatment arm, and constipation, which was more prevalent in the placebo arm.
OncoMed plans to present full study findings, including results from the biomarker analyses, at a future scientific conference.
Filed Under: Drug Discovery