On August 8, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the discontinuation of the Phase 3 KeyVibe-008 trial based on the recommendation of an independent Data Monitoring Committee (DMC) (Press release, Merck & Co, AUG 8, 2024, View Source [SID1234645614]). The trial is evaluating the investigational fixed-dose combination (coformulation) of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA), Merck’s anti-PD-1 therapy, in combination with chemotherapy compared to atezolizumab in combination with chemotherapy, for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). At a pre-planned analysis, data showed that the primary endpoint of overall survival (OS) met the pre-specified futility criteria. Additionally, when compared to patients in the control arm, patients in the vibostolimab and pembrolizumab fixed-dose combination arm experienced a higher rate of adverse events (AEs) and immune-related AEs. A comprehensive analysis of this study is ongoing.

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Merck is notifying study investigators of the decision and that patients should stop ongoing treatment with the fixed-dose combination of vibostolimab and pembrolizumab and be offered the option to be treated with atezolizumab. Results will be shared with the scientific community.

"Small cell lung cancer remains a difficult disease to treat, as evident by the seven percent five-year survival rate and limited advancements in treatment options," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "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."

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations.

In SCLC, Merck and Daiichi Sankyo recently announced that the first patient has been dosed in the IDeate-Lung02 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) in patients with relapsed SCLC versus treatment of physician’s choice of chemotherapy. Merck and Daiichi Sankyo also expanded their existing global co-development and co-commercialization agreement for three investigational DXd antibody-drug conjugates to include Merck’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager that is currently being evaluated in a Phase 1/2 clinical trial (NCT04471727). The companies are planning to evaluate MK-6070 in combination with I-DXd in certain patients with SCLC, as well as other potential combinations. Merck obtained MK-6070 through its acquisition of Harpoon Therapeutics.

Ongoing Phase 3 studies evaluating the vibostolimab and pembrolizumab fixed-dose combination in lung cancer, which are routinely monitored by external data monitoring committees, include KeyVibe-003, KeyVibe-006 and KeyVibe-007. Interim external data monitoring committee safety reviews have not resulted in any study modifications to date and the studies are undergoing ongoing comprehensive safety monitoring.

About KeyVibe-008

KeyVibe-008 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05224141) evaluating a fixed-dose combination of vibostolimab and pembrolizumab (MK-7684A) in combination with etoposide and platinum chemotherapy followed by the vibostolimab and pembrolizumab fixed-dose combination versus atezolizumab in combination with etoposide and platinum chemotherapy followed by atezolizumab for the first-line treatment of patients with ES-SCLC. The primary endpoint is OS, and key secondary endpoints include progression-free survival, objective response rate, duration of response, all as assessed by blinded independent central review (BICR). The trial enrolled 460 patients who were randomized (1:1) to receive:

Vibostolimab/pembrolizumab fixed-dose combination (pembrolizumab 200 mg and vibostolimab 200 mg intravenously [IV] every three weeks [Q3W] for four cycles) in combination with etoposide and platinum chemotherapy (carboplatin or cisplatin) Q3W for a total of approximately 12 weeks followed by additional cycles of the vibostolimab/pembrolizumab fixed-dose combination until any of the conditions for discontinuation are met; or
Atezolizumab (1,200 mg Q3W) in combination with etoposide and platinum chemotherapy (carboplatin or cisplatin) Q3W for a total of approximately 12 weeks followed by additional cycles of atezolizumab until any of the conditions for discontinuation are met.
About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.48 million new cases and 1.8 million deaths from lung cancer globally. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. The two main types of lung cancer are non-small cell and small cell. Small cell lung cancer accounts for about 15% of all lung cancers. Patients with small cell lung cancer have a particularly poor prognosis, with an estimated five-year survival rate of 7% for patients in the United States with any stage of the disease. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.