Merck stops anti-TIGIT combo in melanoma trial

Merck (MSD) has decided to terminate the coformulation arm of its phase 3 melanoma trial involving Keytruda and the investigational anti-TIGIT antibody, vibostolimab, due to a high rate of patient discontinuation. This decision comes after an analysis indicated that the combination therapy was unlikely to achieve its primary endpoint of recurrence-free survival, primarily because of immune-mediated adverse effects.

The KeyVibe-010 trial aimed to evaluate the effectiveness of combining vibostolimab, an anti-TIGIT antibody, with Keytruda, Merck’s widely successful anti-PD-1 therapy, versus Keytruda alone. The study focused on patients with high-risk melanoma (stage IIB-IV) who had undergone resection. The primary goal was to improve recurrence-free survival rates. However, the pre-planned analysis revealed that the combination therapy had little chance of meeting this endpoint due to adverse immune responses.

Given these findings, Merck is now unblinding the study and recommending patients in the combination arm to transition to treatment with Keytruda alone. This move aims to provide a safer therapeutic option for these patients while still utilizing a proven anti-cancer agent.

Vibostolimab operates by blocking the TIGIT receptor, which prevents it from binding to its ligands, CD112 and CD155. This action activates T lymphocytes, which are crucial in attacking and destroying tumor cells. Despite the promising mechanism, the adverse immune reactions observed in the KeyVibe-010 trial necessitated a reevaluation of its use in combination with Keytruda.

Merck has been extensively researching the vibostolimab-Keytruda combination across various cancer types, involving over 3,000 patients. These studies aim to determine whether the combination can provide a significant therapeutic benefit over existing treatments.

In December, Merck reported mixed results from another trial involving vibostolimab and Keytruda in combination with chemotherapy. This phase 2 trial focused on patients with metastatic non-small cell lung cancer. Although the combination extended median progression-free survival by 2.4 months compared to chemotherapy alone, it did not achieve statistical significance, raising further questions about the overall efficacy of the combination therapy.

The recent developments in the KeyVibe-010 trial underscore the complexities and challenges involved in developing combination therapies for cancer treatment. While the concept of combining different mechanisms of action to enhance therapeutic outcomes is compelling, ensuring patient safety remains paramount. Merck's decision to halt the combination arm of the trial and pivot to a safer treatment option reflects its commitment to patient welfare and scientific rigor.

In summary, Merck’s decision to end the coformulation arm of the KeyVibe-010 trial highlights the difficulties in balancing efficacy and safety in cancer therapies. Despite the setback, ongoing research and trials will continue to shape the future of cancer treatment, leveraging both existing and novel therapeutic approaches.