Merck is winding down a late-stage test of its anti-TIGIT candidate vibostolimab in small-cell lung cancer after it showed early signs of poor efficacy, in another blow to the TIGIT space.
The Phase 3 KeyVibe-008 trial was investigating a fixed-dose combination of vibostolimab with Keytruda plus standard-of-care chemotherapy. These therapies were being compared against Roche’s Tecentriq and chemotherapy in the trial that recruited 460 people with first-line extensive-stage SCLC.
Results from a planned analysis showed that the overall survival primary endpoint met pre-specified futility criteria, which means the trial has a low chance of success, Merck said in a Thursday release. Also, patients in the treatment arm had a higher rate of side effects — including immune-related issues — compared with those in the control arm.
Merck is conducting a “comprehensive analysis” of the data and patients in the treatment arm will be given the option to switch over to Tecentriq plus chemotherapy.
The past month has seen several setbacks in the TIGIT space. In July, Roche’s tiragolumab failed a Phase 3 study in certain non-small cell lung cancer patients and, later that month, the company axed two other trials of tiragolumab in light of the NSCLC failure. Earlier this week, Bristol Myers Squibb handed back a TIGIT bispecific drug to Agenus, ending a partnership deal that started in 2021.
As for Merck, the announcement marks the third disappointment for its TIGIT and PD-1 duo in cancer in recent years. In May, a high number of patient dropouts due to immune side effects forced the company to shutter its Phase 3 KeyVibe-010 trial in people with resected, high-risk stage IIB-IV melanoma. In March last year, the regimen failed the open-label portion of a Phase 2 study setting it against chemotherapy in people with metastatic NSCLC.
But Merck isn’t quite done with TIGIT just yet. It still has three Phase 3 studies of vibostolimab plus Keytruda in various settings of lung cancer, including KeyVibe-003, KeyVibe-006 and KeyVibe-007. Interim analyses in these studies have not yet led to any modifications, according to the company.
As for its SCLC efforts, the drugmaker and partner Daiichi Sankyo dosed the first patient in the Phase 3 IDeate-Lung02 trial of ADC candidate ifinatamab deruxtecan in participants with relapsed disease. In January, Merck added another SCLC contender to its pipeline through its $680 million acquisition of Harpoon Therapeutics and its T cell engager asset, HPN328.
SCLC makes up around 15% of all lung cancer cases and has a particularly poor prognosis with a five-year survival rate of just 7% for patients in the US, according to Merck.