Merck Discontinues KeyVibe-008 Trial of Vibostolimab/Pembrolizumab Plus Chemo in ES-SCLC

The phase 3 KeyVibe-008 trial (NCT05224141) evaluating the fixed-dose combination of vibostolimab (MK-7684) and pembrolizumab (Keytruda) plus chemotherapy for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) has been discontinued following a recommendation from an independent data monitoring committee, according to an announcement from Merck.¹

The combination was being evaluated against atezolizumab (Tecentriq) plus chemotherapy. Findings from a preplanned interim analysis showed that the primary end point of overall survival (OS) met the prespecified futility criteria. Furthermore, higher rates of adverse effects (AEs) and immune-related AEs were reported in patients treated with the combination of vibostolimab, pembrolizumab, and chemotherapy.

Merck is informing study investigators that patients in the experimental arm should halt ongoing treatment and be offered the opportunity to cross over to receive atezolizumab plus chemotherapy. Full data from the study will be shared with the scientific community at a later date and a comprehensive analysis of study data is ongoing.

“SCLC remains a difficult disease to treat, as evident by the 7% 5-year survival rate and limited advancements in treatment options,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated in a news 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.”

Vibostolimab is an investigational humanized anti-TIGIT antibody intended to restore antitumor activity via blocking the TIGIT receptor from binding to the CD112 and CD155 ligands. This allows for the activation of T lymphocytes, which assist in the destruction of tumor cells.

The randomized, double-blind KeyVibe-008 trial enrolled patients at least 18 years of age with histologically or cytologically confirmed stage IV ES-SCLC in the first line. Patients were required to have measurable disease per RECIST 1.1 criteria and a predicted life expectancy of more than 3 months.²

Key exclusion criteria included poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease; prior treatment for SCLC; the expected requirement for any other antineoplastic therapy for SCLC while on the study; treatment with a live or live-attenuated vaccine within 30 days of first study treatment; known active central nervous system metastases and/or carcinomatous meningitis; and a history of noninfectious pneumonitis/interstitial lung disease (ILD) that required steroids or current pneumonitis/ILD.

The study enrolled 460 patients who were randomly assigned 1:1 to receive pembrolizumab at 200 mg plus vibostolimab at 200 mg, etoposide, and platinum chemotherapy with carboplatin or cisplatin once every 3 weeks for 4 cycles, followed by vibostolimab plus pembrolizumab; or atezolizumab at 1,200 mg in combination with etoposide and platinum chemotherapy once every 3 weeks for 4 cycles, followed by atezolizumab alone. Patients remained on treatment until any discontinuation criteria were met.¹

Along with the primary end point of OS, secondary end points included progression-free survival, objective response rate, duration of response, safety, and quality of life.²

Other studies evaluating the fixed-dose combination of vibostolimab and pembrolizumab for the treatment of patients with non–small cell lung cancer are ongoing, including the phase 3 KeyVibe-003 (NCT04738487), KeyVibe-006 (NCT05298423), and KeyVibe-007 (NCT05226598) trials.¹

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://www.merck.com/news/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/
2. Pembrolizumab/​vibostolimab (MK-7684A) or atezolizumab in combination with chemotherapy in first line treatment of extensive-stage small cell lung cancer (MK-7684A-008, KEYVIBE-008). ClinicalTrials.gov. Updated May 8, 2024. Accessed August 8, 2024. https://clinicaltrials.gov/study/NCT05224141