OncoMed is halting clinical development of its anticancer stem cell drug demcizumab (anti-DLL4, OMP-21M18) after a Phase II combination therapy study in front-line nonsquamous, non-small-cell lung cancer (NSCLC) failed to meet its primary endpoints.

The disappointing results come just weeks after the firm announced the failure of demcizumab in the Phase II YOSEMITE pancreatic cancer trial, the failure of its Phase II PINNACLE study evaluating the anti-Notch2/3 candidate tarextumab as combination therapy in small-cell lung cancer, and partner Bayer’s decision not to exercise its option to license the two Wnt pathway inhibitors vantictumab and ipafricept. Last month, OncoMed reported that it would cut its workforce by 50% to cut costs.

The failed Phase II DENALI study reported today had been evaluating demcizumab in combination with carboplatin and pemetrexed, compared with placebo plus carboplatin and pemetrexed, as front-line therapy for nonsquamous NSCLC. The study had stopped enrolling at 82 out of a projected 200 patients due to what OncoMed calls “the evolving treatment landscape in NSCLC.” Data from the 82 trial participants showed that not only did the trial fail to meet its primary endpoint of overall response rate (ORR), but that outcomes were better for patients in the placebo group than for those in the demcizumab treatment group. The ORR was 28% in the demcizumab group, compared with 52% in the placebo group, and the clinical benefit rate (a rate of complete and partial repsonses and stable free diseases) was 79% for the demcizumab group and 92% of the placebo group, while median progression-free survival rates were 5.5 months and 8.7 months for the demcizumab and placebo arms, respectively.

OncoMed said it will now discontinue dosing all patients in demcizumab trials, including a Phase Ib study combining the drug with pembrolizumab, and will review the program with partner Celgene.

Celgene and OncoMed agreed to a $177.25 up-front cash and equity-based deal to jointly develop and commercialize up to six anticancer stem cell products from the OncoMed pipeline, including demcizumab. The agreement, signed at the end of 2013, gave Celgene an exclusive option to license demcizumab during or after the completion of specific OncoMed-conducted Phase II studies. OncoMed could potentially have received option exercise, development, regulatory, and commercial payments from Celgene of $790 million related to demcizumab development.

Commenting on the firm’s Q1 financial results and failure of the DENALI study, Paul J. Hastings, OncoMed’s chairman and CEO, said the firm would continue to progress additional programs in the Celgene collaboration, which could result in $98 million in potential opt-in payments during the next 2 years. 

Reporting the firm’s Q1 financial results, Hastings also noted that the firm had cash and short-term investments of $156.9 million, and would continue to develop its immune-oncology anti-TIGIT (T-cell immunoreceptor with Ig and ITIM domains) antibody candidate, its GITRL-Fc trimer, and other immune-oncology discovery programs. “With more than 2 years cash, we are dedicated to advancing our pipeline while exploring partnering opportunities to advance all of our programs.”

A Phase Ia study with the anti-TIGIT candidate OMOP-313M32 was started last week in patients with advanced or metastatic solid tumors.








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