Merck Cancels Two Keytruda Phase III Cancer Trials After Poor Results

Merck announced on Thursday that it will cease two Phase III studies focusing on Keytruda (pembrolizumab) for treating lung and skin cancers due to unsatisfactory results. This decision follows a series of setbacks for the company's blockbuster PD-1 inhibitor in recent clinical trials.

The first discontinued trial, KEYNOTE-867, aimed to evaluate Keytruda in conjunction with stereotactic body radiotherapy (SBRT) in patients with stage I or II non-small cell lung cancer (NSCLC). An interim analysis revealed that the Keytruda and SBRT combination did not significantly enhance event-free survival or overall survival compared to SBRT alone. Additionally, the combination led to a higher incidence of adverse events, including fatalities, making the risk-benefit profile unfavorable for continuing the study.

The second terminated trial, KEYNOTE-630, assessed adjuvant Keytruda in patients with high-risk, locally advanced cutaneous squamous cell carcinoma (cSCC) who had previously undergone surgery and radiation. An independent data monitoring committee recommended halting the trial due to futility, as Keytruda did not achieve the primary endpoint of recurrence-free survival. Although overall survival, a key secondary endpoint, was not formally tested, preliminary data did not favor the Keytruda regimen. The safety profile of Keytruda in this trial was consistent with earlier studies.

Merck has informed the study investigators about the discontinuations, advising enrolled patients to consult their healthcare providers for alternative treatments. The company will continue analyzing data from these trials and share the findings with regulatory authorities and the scientific community.

This announcement adds to a string of clinical challenges for Keytruda. Earlier this month, Merck halted a Phase III trial of Keytruda combined with the anti-TIGIT antibody vibostolimab and chemotherapy for first-line treatment of extensive-stage small cell lung cancer. The decision followed a data monitoring committee's assessment that the overall survival data met futility criteria. Safety concerns were also noted, with the combination therapy leading to higher toxicity rates, including immune-related adverse events.

In May 2024, Merck discontinued another Phase III trial evaluating Keytruda and vibostolimab in patients with resected high-risk melanoma. A pre-planned analysis flagged a high rate of study dropouts, primarily due to immune-mediated adverse events, prompting the termination. That same month, Keytruda failed a Phase III study in endometrial cancer. When used as an adjuvant treatment with chemotherapy, with or without radiotherapy, Keytruda did not significantly improve disease-free survival compared to placebo in patients with newly diagnosed, high-risk endometrial cancer.

Despite these setbacks, Merck remains committed to understanding the data from these trials and will continue to collaborate with regulatory bodies and the scientific community to optimize patient outcomes.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!