Merck announced on Thursday Stopping two late-stage studies The company is looking at its blockbuster PD-1 inhibitor Keytruda (pembrolizumab) as a treatment for lung and skin cancer, but the prognosis is poor.
The drugmaker is halting its Phase III KEYNOTE-867 study in non-small cell lung cancer (NSCLC) after an interim analysis showed that Keytruda, when combined with stereotactic body radiation therapy (SBRT), did not significantly improve event-free or overall survival in patients with stage I or II disease.
In terms of safety, Keytruda plus SBRT was associated with a higher rate of adverse events, including those leading to death, than placebo plus SBRT. Given these results, Merck said, the benefit/risk profile of Keytruda therapy in this indication does not support continuing the study.
The company is also completing the Phase 3 KEYNOTE-630 trial evaluating Keytruda as an adjuvant treatment for patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) who have undergone surgery and radiation therapy, using a placebo as the comparator.
During a pre-analysis, an independent data monitoring committee recommended KEYNOTE-630 be discontinued for futility because Keytruda failed to meet statistical significance for the primary endpoint of recurrence-free survival. The key secondary endpoint of overall survival was not formally examined, but Merck said the numbers at the time of the pre-analysis were not in favor of Keytruda.
The safety profile of Keytruda in KEYNOTE-630 was consistent with that established in previous studies.
Merck has notified the study investigators of the decision to discontinue the trials, and enrolled patients are encouraged to coordinate with their healthcare providers regarding alternative treatment options. The company will continue to analyze data from the two trials and share its findings with regulatory authorities and the scientific community at large.
Thursday’s announcement marks a continuing loss for Keytruda, which has faced clinical challenges in recent months. Earlier this month, Merck Phase III studies had to be halted The PD-1 inhibitor is used in combination with the anti-TIGIT antibody vibostolimab and chemotherapy as first-line treatment for extensive-stage small cell lung cancer.
At the time, the Data Monitoring Committee determined that Keytruda’s overall survival data in this indication met the criteria for futility. Safety was also an issue, with patients receiving the combination experiencing higher rates of toxicity, including immune-related toxicities.
May 2024, Merck Another Phase 3 trial was halted The study looked at Keytruda and vibostolimab in patients with resected, high-risk melanoma. The drugmakers noted that a preplanned analysis showed high study dropout rates, primarily due to immune-mediated adverse events.
That same month, Merck announced that Keytruda Failed Phase III trials In endometrial cancer, PD-1 inhibitors did not significantly improve disease-free survival compared with placebo in patients with newly diagnosed high-risk endometrial cancer when used as adjuvant treatment to chemotherapy with or without radiation therapy.
