Merck has announced the discontinuation of two Phase 3 clinical trials, KEYNOTE-867 and KEYNOTE-630, which were evaluating the efficacy of pembrolizumab (Keytruda) in patients with non-small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma (CSCC), respectively. The decision was based on recommendations from independent Data Monitoring Committees (DMC) after interim analyses showed insufficient clinical benefit.
KEYNOTE-867: Pembrolizumab Plus SBRT in NSCLC
KEYNOTE-867 (NCT03924869) was a double-blind, randomized Phase 3 trial assessing pembrolizumab in combination with stereotactic body radiotherapy (SBRT) for patients with unresected stage I or II NSCLC who were medically inoperable or declined surgery. The trial enrolled approximately 436 patients who were randomized 1:1 to receive either pembrolizumab (200 mg every 3 weeks for up to 17 cycles) plus SBRT or placebo plus SBRT.
The primary endpoint of event-free survival (EFS) and key secondary endpoint of overall survival (OS) were not met at the pre-specified interim analysis. The DMC concluded that pembrolizumab plus SBRT did not demonstrate a significant improvement compared to placebo plus SBRT. Furthermore, the combination therapy was associated with higher rates of adverse events, including those leading to death, leading the DMC to recommend halting the trial.
KEYNOTE-630: Pembrolizumab in Adjuvant CSCC
KEYNOTE-630 (NCT03833167) was a double-blind, randomized Phase 3 trial investigating pembrolizumab as adjuvant therapy in patients with high-risk, locally advanced CSCC who had undergone surgery with or without positive margins and completed adjuvant radiotherapy. Approximately 430 patients were randomized to receive either pembrolizumab (400 mg intravenously every 6 weeks for up to 9 cycles) or placebo.
A preplanned analysis indicated that pembrolizumab did not cross the boundary for statistical significance in recurrence-free survival (RFS), the trial’s primary endpoint. Although overall survival (OS), a key secondary endpoint, was not formally tested, initial data did not favor pembrolizumab over placebo. The DMC recommended discontinuing the trial for futility, as the risk/benefit profile did not support continuing the study. The safety profile of pembrolizumab was consistent with previous findings.
Company Statement
According to a press release, Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated, “Our understanding of cancer and how it can be treated has rapidly evolved in recent years, but unmet needs remain across different types of cancer and stages of disease. That is why we continue our rigorous exploration of innovative treatment approaches in cancers with high unmet need, such as NSCLC and cutaneous squamous cell carcinoma, with the goal to help even more patients. We are extremely grateful to all of the patients, caregivers and investigators for their participation in these studies.”
Ongoing Analysis and Future Steps
Merck has informed the investigators of both trials about the discontinuations and advised patients to consult with their treatment teams regarding available options. Data analyses for KEYNOTE-867 and KEYNOTE-630 are ongoing, and the company plans to share the results with the scientific community and regulatory agencies.
