OncoMed's experimental lung cancer drug tarextumab misses endpoints of Phase II study

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Shares in OncoMed Pharmaceuticals declined as much as 30 percent Monday after the company announced top-line Phase II data showing that a combination of its experimental drug tarextumab plus chemotherapy failed to meet the primary endpoint of significantly slowing progression-free survival (PFS) in patients with small-cell lung cancer (SCLC), compared with chemotherapy alone. Results from the PINNACLE trial also showed that the anti-Notch2/3 drug did not achieve the secondary goal of overall survival (OS) and biomarkers reflective of Notch pathway gene activation.

Further, the drugmaker announced it is terminating enrolment in a Phase Ib study of the anti-Notch1 drug brontictuzumab in combination with Taiho Oncology's Lonsurf (trifluridine/tipiracil) for the third-line treatment of patients with colorectal cancer, as the combination was "not tolerable" in this population. The news follows OncoMed's disclosure last week that its experimental drug demcizumab failed the mid-stage YOSEMITE study of patients with treatment-naïve metastatic pancreatic cancer, and that Bayer had decided against licencing the investigational Wnt inhibitors vantictumab and ipafricept for "strategic reasons."

OncoMed CEO Paul Hastings remarked "based on the events of today and last week, we will be undertaking a comprehensive portfolio prioritisation review immediately." He said the "immediate task ahead is to thoroughly examine the available data, our resources and the opportunities to re-focus our efforts."

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The PINNACLE trial randomised 145 previously untreated patients with extensive-stage SCLC to receive tarextumab in combination with etoposide plus carboplatin or cisplatin, or to receive chemotherapy plus placebo.

According to OncoMed, results showed that median PFS in the tarextumab arm was 5.6 months, versus 5.5 months in the placebo group. Meanwhile, median OS was 9.3 months among tarextumab-treated patients, compared with 10.3 months for those who only received chemotherapy. Additionally, overall response rates in the tarextumab and placebo groups were 68.5 percent and 70.8 percent, respectively. OncoMed also noted that five individual Notch biomarkers had failed to identify a definitive subset of patients with a treatment effect on either PFS or OS. 

Commenting on the news, Leerink Partners analyst Michael Schmidt remarked "OncoMed's management will need to focus on rebuilding the research and development pipeline in a capital-efficient manner."

Last year, the company said an independent data safety monitoring board had concluded that tarextumab was unlikely to achieve the primary endpoint of OS in the Phase II ALPINE study of patients with pancreatic cancer. The therapy is being developed as part of a 2007 agreement with GlaxoSmithKline, with the latter having an option to obtain an exclusive license to the drug through completion of the proof-of-concept Phase II trials.

For related analysis, see ViewPoints: Double whammy for OncoMed calls CSC platform into question.