Adding the anti-Dll4 antibody demcizumab to standard-of-care — Abraxane (protein-bound paclitaxel) plus gemcitabine — does not improve progression-free or overall survival in newly diagnosed metastatic pancreatic cancer patients, compared to standard-of-care.
The recent data from OncoMed‘s Phase 2 YOSEMITE trial (NCT02289898) show the trial failed to meet its primary and secondary endpoints. Based on the findings, the company announced it will discontinue the trial and has plans to discontinue any enrollment in other ongoing demcizumab trials.
“Patients in all three arms of the Phase 2 YOSEMITE trial surpassed the published median overall survival rates for Abraxane plus gemcitabine in first-line metastatic pancreatic patients,” Paul J. Hastings, chairman and CEO of OncoMed Pharmaceuticals, said in a press release. “While the interim median overall survival was 13.2 months in the pooled demcizumab arms, the interim median overall survival of Abraxane plus gemcitabine was not reached at the time of these analyses.
“Based on the lack of benefit over standard-of-care, which performed remarkably well, we will be discontinuing this trial,” he added. “We will conduct additional analyses, together with our partner, Celgene, to understand these outcomes. We will also discontinue any additional enrollment in our other ongoing demcizumab trials and conduct analyses of the data from those trials as planned.”
OncoMed is currently conducting a Phase 2 trial evaluating demcizumab in patients with non-squamous non-small cell lung cancer (NSCLC). The randomized, double-blind, three-arm DENALI study (NCT02259582) was designed to enroll 200 newly diagnosed patients with metastatic non-squamous NSCLC, whose tumors do not have an EGFR or ALK mutation.
Patients were randomized to receive either demcizumab combined with Paraplatin (carboplatin) and Alimta (pemetrexed), or Paraplatin and Alimta alone. The trial has completed enrollment and data is expected in the second half of 2017.
OncoMed also is testing demcizumab in combination with Keytruda (pembrolizumab) in patients with locally advanced metastatic solid tumors (NCT02722954), including lung cancer patients.
The company has another experimental therapy, tarextumab, being evaluated as a treatment for lung cancer. Tarextumab is a fully human monoclonal antibody that targets the Notch 2 and Notch 3 receptors, and appears to have anti-cancer stem cell effects and to disrupt tumor blood vessels.
The Phase 2 PINNACLE trial (NCT01859741) enrolled 145 patients with extensive-stage small cell lung cancer who had not received prior treatment. Participants were randomized to receive tarextumab every three weeks in combination with six cycles of etoposide and platinum therapy, followed by tarextumab maintenance until disease progression, or six cycles of standard chemotherapy and a placebo.
The study’s primary endpoint is progression-free survival, and secondary endpoints include overall survival and overall response rate.
“OncoMed remains focused on completing and analyzing the results of the two randomized Phase 2 clinical trials, PINNACLE and DENALI, that are anticipated in the first half of this year and in continuing the advancement of our portfolio of biotherapeutic candidates,” said Hastings.