Merck's Phase II KeyVibe-002 Trial of PD-1/TIGIT Bispecific MK-7684A Fails to Meet PFS Endpoint in NSCLC vs. Docetaxel

On March 16, MSD announced the Phase II results of the PD-1+TIGIT combination drug MK-7684A for the treatment of metastatic non-small cell lung cancer (NSCLC).Non-registeredLatest Results of KeyVibe-002 Study. The open-label portion showed that, compared to docetaxel treatment, MK-7684AMonotherapyNo statistically significant improvement was observed in the primary endpoint of progression-free survival (PFS), and MK-7684A numerically showed less efficacy compared to docetaxel.

MK-7684A is a combination drug containing vibostolimab, which targets TIGIT, and pembrolizumab, which targets PD-1. Vibostolimab restores anti-tumor activity by blocking the binding of the TIGIT receptor to its ligands (CD112 and CD155), thereby activating T lymphocytes to help eliminate tumor cells.

KeyVibe-002 Study (NCT04725188) is a randomized, partially blinded Phase II clinical trial designed to evaluate the efficacy and safety of MK-7684A in treating patients with metastatic NSCLC who experienced disease progression after prior immunotherapy and platinum-based doublet chemotherapy. The study has two primary objectives: 1) to assess the efficacy of MK-7684A monotherapy compared to standard docetaxel treatment; 2) to blindly evaluate the efficacy of MK-7684A combined with docetaxel versus docetaxel alone.

The study enrolled 255 patients who were randomly assigned to three independent study groups (1:1:1): Arm 1 received MK-7684A (pembrolizumab 200 mg + vibostolimab 200 mg/20mL, administered intravenously once every 3 weeks until discontinuation criteria were met or 35 cycles were completed); Arm 2 received MK-7684A in combination with docetaxel; and Arm 3 received placebo in combination with docetaxel.

Results from the open-label portion showed that MK-7684A monotherapy did not achieve a statistically significant improvement in the primary endpoint of PFS compared to docetaxel treatment, and numerically, MK-7684A demonstrated less efficacy than docetaxel. Merck & Co., Inc. is notifying investigators that patients in this study arm should switch to standard-of-care treatment unless the physician believes the patient could benefit from continued MK-7684A monotherapy.

The study will continue to evaluate the efficacy of MK-7684A in combination with docetaxel compared to docetaxel alone. The safety profile of MK-7684A is consistent with the safety profiles of vibostolimab and pembrolizumab, with no new safety signals observed.

MSD has an extensive clinical development program evaluating the efficacy and safety of MK-7684A as a monotherapy or in combination with other drugs in more than 4,000 patients. Ongoing Phase III studies in lung cancer include KeyVibe-003, KeyVibe-006, KeyVibe-007, and KeyVibe-008, as well as KeyVibe-010 for melanoma.

MSD is not the only company that has stumbled on the TIGIT project. Tiragolumab is a key clinical candidate that Roche has high hopes for. However, Tiragolumab has already missed the PFS endpoint in two important lung cancer indications.

In March 2022, Roche announced that the Phase III SKYSCRAPER-02 study of Tiragolumab in combination with Atezolizumab and chemotherapy as a first-line treatment for extensive-stage small cell lung cancer did not meet the co-primary endpoint of PFS.

In May of the same year, more bad news came: the second Phase III trial of Tiragolumab failed. The SKYBUILDINGER-01 study did not demonstrate that the combination of Tiragolumab and Atezolizumab extended PFS compared to Atezolizumab monotherapy as a first-line treatment for PD-L1 high-expression NSCLC patients.

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