Bad vibes continue for Merck

Yesterday Merck admitted that its Tigit-Keytruda coformulation MK-7684A was numerically inferior to chemo in the phase 2 Keyvibe-002 lung cancer trial, and the question now is what that means for other studies of the Tigit, vibostolimab. The trial was a long shot since patients had already failed on one checkpoint inhibitor and chemotherapy, and following the disappointing performance of vibostolimab in Keynote-001 three years ago. Data from the open-label arm of Keyvibe-002 showed that the vibostolimab-Keytruda combo was inferior to docetaxel on the primary endpoint of PFS in NSCLC patients who had progressed on anti-PD(L)1 and platinum-based chemo. Keyvibe-002 also has a blinded comparison of the combo plus docetaxel versus docetaxel alone, and Merck is continuing this. But attention will now shift to the much bigger phase 3 study Keyvibe-003, in the first-line treatment of NSCLC patients with PD(L)1 expression of at least 1%, and while this is a different setting the chance of success now looks even slimmer. That said, both Mizuho and SVB analysts point to the Keymaker-U02 substudy 02C in neoadjuvant stage III melanoma, data from which is expected at AACR next month, as giving closer read-through to the Keyvibe programme in an earlier setting. 

Selected Keyvibe trials of Merck's vibostolimab
Trial Arms Setting PCD
Keyvibe-001* Uncontrolled PD-(L)1-naive NSCLC Disappointed Sep 2020
Keyvibe-002** Vibostolimab + Keytruda +/- chemo, vs chemo PD-L(1)/chemo-experienced NSCLC  Failed Mar 2023
Keyvibe-003 Vibostolimab + Keytruda, vs Keytruda 1L PDL(1)+ NSCLC w PD(L)1 expression >1% Apr 2026
Keyvibe-006 Vibostolimab + Keytruda + CRT, vs Imfinzi + CRT Stage III inoperable NSCLC Sep 2028
Keyvibe-007 Vibostolimab + Keytruda + chemo, vs Keytruda + chemo 1L metastatic NSCLC Nov 2025
Keyvibe-008 Vibostolimab + Keytruda + chemo, vs Tecentriq + chemo 1L extensive-stage SCLC May 2025
Keyvibe-010 Vibostolimab + Keytruda, vs Keytruda Adjuvant treatment in resected stage II-IV melanoma  Oct 2027
*Ph1 trial. **Ph2 trial. All others Ph3. Source: Evaluate Pharma, 

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