OncoMed Pharmaceuticals has announced an update on its phase 2 ALPINE trial of the pancreatic cancer drug tarextumab after a preplanned interim efficacy assessment by an independent data safety monitoring board (DSMB). The DSMB evaluated data from 172 patients treated as of a data cutoff date of January 6, 2016.
The DSMB informed OncoMed of several findings regarding the trial’s futility, including a statistically significant worsening of the response rate and of progression-free survival (PFS) in the treatment arm. Moreover, a strong trend toward a lack of benefit in the treatment arm for overall survival (OS) suggested a low probability of achieving a statistically significant OS benefit, based on analyses reviewed by the DSMB.
Based on this information, OncoMed is in the process of unblinding the trial to assess the current results and to determine appropriate next steps.
The ALPINE (Antibody Therapy in First-Line Pancreatic Cancer Investigating Anti-Notch Efficacy and Safety) trial was a randomized, double-blind study designed to evaluate the efficacy of tarextumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension [albumin bound], Celgene) plus gemcitabine in patients with previously untreated stage IV pancreatic cancer. The study, which completed enrollment of 177 patients in August 2015, compared OS with tarextumab (15 mg/kg every two weeks) or placebo, both administered in combination with Abraxane plus gemcitabine. Secondary and exploratory endpoints, including PFS, the response rate, pharmacokinetics, and safety, are to be evaluated.
Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab has two mechanisms of action: 1) by downregulating Notch pathway signaling, tarextumab appears to have anticancer stem-cell effects, and 2) tarextumab affects pericytes, thereby impacting the stromal and tumor microenvironment.
In addition to the ALPINE trial, the PINNACLE (Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Platinum Therapy in Subjects With Untreated Extensive-Stage Small-Cell Lung Cancer) trial is evaluating tarextumab in combination with etoposide and cisplatin or in combination with etoposide and carboplatin in patients with extensive-stage small-cell lung cancer.
Source: BioSpace; January 25, 2016.