Out with the old, in with the new. The end of the year in biopharma is typically marked by pipeline clear-outs, and 2024 is proving it’s no different.
In a day that already included discontinuations from Roche and Foghorn Therapeutics, Merck & Co. rounded out Monday by announcing the termination of two late-stage cancer assets.
The New Jersey-based drugmaker is ending development of anti-TIGIT antibody vibostolimab and anti-LAG-3 antibody favezelimab, according to a Dec. 16 release shared after market close.
Vibostolimab was being tested as part of a fixed-dose combination with Merck's megablockbuster oncology drug Keytruda in a pair of phase 3 trials, dubbed KeyVibe-003 and KeyVibe-007. Both studies are evaluating the investigational combo in certain patients with non-small cell lung cancer (NSCLC).
The discontinuation is based on a recommendation from an independent data monitoring committee, according to Merck.
In a preplanned analysis, both trials met the prespecified futility criteria for the primary endpoint of overall survival. The safety profile was consistent with that observed in previously reported studies, with more immune-related adverse events observed for the fixed-dose combination than with Keytruda alone.
Considering the totality of the data, Merck is also discontinuing the phase 3 KeyVibe-006 trial plus other vibostolimab studies. KeyVibe-006 is a randomized, open-label study of the investigational fixed-dose with chemoradiotherapy for patients with stage 3 NSCLC.
Last December, a combination of vibostolimab and Keytruda was found to be less effective than the chemotherapy docetaxel in a phase 2 trial in previously treated metastatic NSCLC.
Earlier in the year, the Big Pharma bailed on a phase 3 test of the anti-TIGIT antibody after a high discontinuation rate rendered the trial's success unlikely. The study had been examining vibostolimab with Keytruda as an adjuvant treatment for patients with resected high-risk melanoma.
Then there’s favezelimab. The asset was being tested in a phase 3 trial in combination with Keytruda for patients with advanced classical Hodgkin lymphoma whose disease has progressed after prior anti-PD-1 therapy. Merck is stopping enrollment of the trial, dubbed KEYFORM-008, but giving trial participants the choice to continue treatment until the study is done.
While the results from KEYFORM-008 are not available yet, Merck made the decision after “a thorough evaluation of data from the favezelimab clinical program,” according to the release. The choice doesn't stem from any safety concerns about the fixed-dose combination, Merck said.
The discontinuation follows a late-stage miss for the asset in microsatellite stable (MSS) metastatic colorectal cancer. Reported in September, the drugmaker found a fixed-dose combination of Keytruda and favezelimab failed to improve overall survival, closing off one avenue for bringing checkpoint inhibitors to MSS colorectal cancer.
The Big Pharma is now informing trial investigators of the discontinuations and recommends that patients speak with their physicians about next steps. Data analyses for the trials are ongoing, with the findings expected to be shared at a later date.