Phase 3 KeyVibe-008 Study in SCLC to Stop Due to Futility

The phase 3 KeyVibe-008 study (NCT05224141) investigating the fixed-dose combination of vibostolimab and pembrolizumab (Keytruda) for the first-line treatment of extensive-stage small cell lung cancer (SCLC) will not continue due to futility, based on the recommendation of an independent data monitoring committee.¹

At the time of a planned analysis, the primary end point of overall survival had met prespecified futility criteria. Further, there was a higher incidence of adverse events (AEs) in the vibostolimab/pembrolizumab arm compared with the control arm of atezolizumab (Tecentriq) and chemotherapy.

Patients will be offered the opportunity to switch to treatment with atezolizumab, and results from these findings will be shared with the medical community.

“Small cell lung cancer remains a difficult disease to treat, as evident by the 7% 5-year survival rate and limited advancements in treatment options,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in a press release. “Innovative research plays a critical role in improving our understanding to help patients achieve better outcomes, and while we hoped the results would be different, we remain committed to investigating novel approaches to treat this debilitating disease. We are extremely grateful to all of the patients, caregivers and investigators for their participation in this study.”

About the KeyVibe Studies

Vibostolimab is an investigational anti-TIGIT antibody that restores antitumor activity by blocking the TIGIT receptor from binding to its CD112 and CD155 ligands. This activates T lymphocytes to help degrade tumor cells. The KeyVibe series of studies are investigating vibostolimab in combination with the anti-PD-1 therapy pembrolizumab.

Currently, pembrolizumab is not indicated for the treatment of SCLC; however, over 1600 trials are investigating the agent across cancer types and treatment settings.

In May 2024, the KeyVibe-010 study (NCT05665595) of the combination in resected high-risk melanoma was discontinued due to futility.² While the combination improved progression-free survival vs docetaxel in patients with metastatic non–small cell lung cancer (NSCLC), the improvement was not statistically significant, according to data from the KeyVibe-002 study (NCT04725188) presented at the 2023 European Society for Medical Oncology Immuno-Oncology Congress.³

Three additional phase 3 KeyVibe studies are ongoing.¹ These include KeyVibe-003 (NCT04738487) in metastatic PD-L1-positive NSCLC, KeyVibe-006 (NCT05298423) in stage III NSCLC, and KeyVibe-007 (NCT05226598) in metastatic NSCLC.

REFERENCES:

1. Merck provides update on phase 3 KeyVibe-008 trial evaluating an investigational fixed-dose combination of vibostolimab and pembrolizumab in patients with extensive-stage small cell lung cancer. News release. Merck. August 8, 2024. Accessed August 8, 2024. https://tinyurl.com/yp4sfunb

2. Merck provides update on phase 3 KeyVibe-010 trial evaluating an investigational coformulation of vibostolimab and pembrolizumab as adjuvant treatment for patients with resected high-risk melanoma. News release. Merck. May 13, 2024. Accessed August 8, 2024. https://tinyurl.com/3vd6k9x6

3. Merck announces findings from phase 2 KeyVibe-002 trial evaluating an investigational coformulation of vibostolimab and pembrolizumab in previously treated patients with metastatic non–small cell lung cancer (NSCLC). News release. Merck. December 7, 2023. Accessed August 8, 2024. https://tinyurl.com/3z8wdet2