Merck & Co. has cracked open the casket of its failed phase 2 TIGIT clinical trial, revealing that neither combination featuring its antibody vibostolimab improved progression-free or overall survival (PFS/OS).
The study enrolled patients with metastatic non-small cell lung cancer (NSCLC) with progressive disease after receiving immunotherapy and platinum-doublet chemotherapy. In March, Merck revealed that the combination of vibostolimab and its anti-PD-1 immunotherapy Keytruda was numerically less effective than docetaxel in terms of PFS, the primary endpoint.
Merck dropped the two-drug combination, which it was testing in an open-label arm, and continued to give people vibostolimab, Keytruda and docetaxel in a blinded cohort. The drugmaker shared data on all three arms at the 2023 European Society of Medical Oncology Immuno-Oncology Annual Congress.
Having shared some data last week, Merck followed up with more results at the event itself. The full dataset suggests vibostolimab plus Keytruda is ineffective in the targeted, later-line NSCLC population. PFS in patients who received the two-drug cocktail was 2.7 months, compared to 3.2 months in the docetaxel control arm. OS was 7.5 months for the combo and 8.8 months for the control.
The blinded cohort of patients who received all three drugs fared better, although the improvement over docetaxel alone fell short of statistical significance. PFS in the three-drug cohort was 5.6 months and OS was 10.2 months.
On the safety front, 29.4% of patients who received all three molecules had immune-mediated adverse events and infusion reactions, compared to 12% of their counterparts in the control arm. There were four treatment-related deaths in the three-drug cohort, and one each in the other two groups.
The study is part of a much broader program, which could still show vibostolimab is effective outside of the hard-to-treat population it targeted. KeyVibe-003, a phase 3, first-line NSCLC trial with a primary completion date in 2026, will be a key test of the drug candidate. By the time that trial reads out, Merck could have data from two other phase 3 studies, one in NSCLC and another in small cell lung cancer.
Talking to investors at an event last week, Eliav Barr, chief medical officer at Merck, identified phase 3 data as the key currency in the topsy-turvy TIGIT space. “We have to acknowledge that there have been phase 2 studies that have looked good, and then there's been phase 3s that have been more complex. So, the way I see the compound is we would wait to see phase 3 and go from there,” Barr said.