The pharma continued its clinical losing streak on Thursday with the announcement that it is discontinuing late-stage studies of the anti-PD-1 therapy in non-small cell lung cancer and cutaneous squamous cell carcinoma.
Merck announced on Thursday that it will discontinue two late-stage studies looking at its blockbuster PD-1 inhibitor Keytruda (pembrolizumab) in lung and skin cancer, following poor outcomes.
The pharma is terminating the Phase III KEYNOTE-867 in non-small cell lung cancer (NSCLC) after an interim analysis showed that Keytruda, when administered alongside stereotactic body radiotherapy (SBRT), did not significantly improve event-free survival or overall survival in patient with stage I or II disease.
In terms of safety, the Keytruda plus SBRT combination elicited a higher rate of adverse events, including some that led to death, than placebo plus SBRT. Given these findings, the benefit/risk profile of the Keytruda regimen in this indication does not support pushing through with the trial, according to Merck.
The pharma is also ending the Phase III KEYNOTE-630 study, which looked at adjuvant Keytruda for patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) who had undergone surgery and radiation. Placebo was used as a comparator.
During a pre-analysis, an independent data monitoring committee recommended that KEYNOTE-630 be stopped due to futility after Keytruda failed to meet statistical significance for the primary endpoint of recurrence-free survival. Overall survival, a key secondary outcome, was not formally tested, though figures at the time of the pre-analysis did not favor Keytruda, according to Merck.
Keytruda’s safety profile in KEYNOTE-630 was consistent with what had been established in prior studies.
Merck has notified the study investigators of the termination and enrolled patients are advised to coordinate with their healthcare providers for alternative treatment options. The company will continue to analyze data from the two trials and will share its findings with regulatory authorities and the broader scientific community.
Thursday’s announcement continues a losing streak for Keytruda, which in recent months has run into clinical challenges. Earlier this month, Merck was forced to stop a Phase III study of the PD-1 inhibitor, in combination with the anti-TIGIT antibody vibostolimab and chemotherapy, for the first-line treatment of extensive-stage small cell lung cancer.
At the time, a data monitoring committee found that overall survival data for Keytruda in this indication met the criteria for futility. Safety was also an issue, with patients taking the combo regimen showing a higher rate of toxicities, including some which were immune-related.
In May 2024, Merck discontinued another Phase III trial looking at Keytruda and vibostolimab, this time in patients with resected high-risk melanoma. The pharma noted that a pre-planned analysis flagged a high rate of study dropouts, mostly due to immune-mediated adverse events.
That same month, Merck reported that Keytruda failed a Phase III study in endometrial cancer. When used as an adjuvant treatment with chemotherapy, with or without radiotherapy, the PD-1 blocker failed to significantly improve disease-free survival versus placebo in patients with newly diagnosed, high-risk endometrial cancer.
