Merck Updates on Phase 3 KEYNOTE-867 and KEYNOTE-630 Trials

Merck, known as MSD outside of the U.S. and Canada, has announced the termination of two Phase 3 clinical trials, KEYNOTE-867 and KEYNOTE-630, based on recommendations from independent Data Monitoring Committees (DMCs). 

The KEYNOTE-867 trial was evaluating the efficacy of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, combined with stereotactic body radiotherapy (SBRT) for the treatment of patients with stage I or II non-small cell lung cancer (NSCLC). Despite the initial expectations, the interim analysis revealed that the combination of KEYTRUDA and SBRT did not show improvement in event-free survival (EFS) or overall survival (OS) compared to placebo plus SBRT. Furthermore, the combination treatment was associated with higher rates of adverse events, including fatalities, leading the DMC to recommend discontinuation of the trial due to an unfavorable benefit/risk profile.

The KEYNOTE-630 trial aimed to assess the use of KEYTRUDA as an adjuvant treatment for patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) after surgery and radiation. The DMC advised stopping the trial for futility as the interim analysis indicated that KEYTRUDA did not achieve statistical significance in recurrence-free survival (RFS), the primary endpoint. Additionally, the secondary endpoint, overall survival, did not show favorable results for KEYTRUDA compared to the placebo group. The safety profile of KEYTRUDA in this trial was consistent with its known safety data.

Merck has communicated these findings to the study investigators and recommended that patients involved in the trials consult their physicians for further guidance and treatment options. Although the trials have been terminated, data analysis will continue, and the findings will be shared with the scientific community and regulatory bodies in the future.

Dr. Marjorie Green, Senior Vice President and Head of Oncology at Merck Research Laboratories, emphasized the ongoing commitment to exploring innovative cancer treatments despite the discontinuation of these trials. She acknowledged the rapid advancements in cancer understanding and treatment, highlighting the persisting unmet needs in various cancer types and stages.

KEYNOTE-867 was a double-blind, randomized Phase 3 trial evaluating the efficacy of KEYTRUDA in combination with SBRT in patients with unresected stage I or II NSCLC who were medically inoperable or opted out of surgery. The trial’s primary goal was to assess event-free survival, with overall survival and safety as key secondary endpoints. The study enrolled approximately 436 patients, who were randomized to receive either KEYTRUDA or placebo alongside SBRT.

Similarly, KEYNOTE-630 was a double-blind, randomized Phase 3 trial investigating the role of KEYTRUDA as adjuvant therapy for patients with high-risk locally advanced cSCC post-surgery and radiation. The primary endpoint was recurrence-free survival, with overall survival and safety as key secondary endpoints. The trial included about 430 patients, divided into groups receiving either KEYTRUDA or placebo.

Lung cancer remains the leading cause of cancer deaths worldwide, with NSCLC accounting for about 80% of all lung cancer cases. Early detection and screening are critical, as a significant percentage of lung cancer cases are diagnosed at advanced stages. Cutaneous squamous cell carcinoma, a common non-melanoma skin cancer, has seen rising prevalence due to better detection, increased sun exposure, and aging populations.

Merck continues its efforts in early-stage cancer research, with more than 30 ongoing registrational studies across various cancer types. The goal is to leverage the potential of KEYTRUDA and other treatments in earlier stages of disease to improve patient outcomes.

KEYTRUDA is a humanized monoclonal antibody designed to enhance the immune system's ability to detect and combat cancer cells. It achieves this by blocking the interaction between PD-1 and its ligands, thus activating T lymphocytes. Merck's extensive clinical research program for KEYTRUDA includes over 1,600 trials across various cancers and treatment settings, aiming to understand the factors that predict patient response to the therapy.

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