Merck's PD-1 Miracle Drug Keytruda Faces Setback: Three Studies on Lung and Skin Cancer Announce Failure, Patients at Higher Risk!

On August 29, 2023, Merck officially announced that in view of the unsatisfactory clinical trial data and the efficacy did not meet expectations, it decided to discontinue two phase 3 studies on the PD-1 inhibitor Keytruda (Palizumab) in the treatment of lung and skin cancer, namely KEYNOTE-867 and KEYNOTE-630 studies.

The interim analysis showed that the combination of Keytruda and stereotactic radiotherapy (SBRT) did not significantly improve event-free survival or overall survival in patients with stage I or II non-small cell lung cancer (NSCLC), so Merck decided to terminate the KEYMAT-867 study. The study was designed to evaluate the efficacy of Keytruda in the treatment of NSCLC.

In terms of safety assessment, the combination of Keytruda and SBRT was associated with a higher incidence of adverse events, including some resulting in death, than the combination of placebo and SBRT. Based on these findings, Merck determined that the risk to benefit ratio of Keytruda in this indication does not support continuation of the trial.

At the same time, Merck also terminated the KEYKEY-630 Phase 3 study, which was looking at Keytruda as an adjunct therapy for patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) undergoing surgery and radiation therapy, versus a placebo. During the pre-analysis period, Keytruda failed to achieve statistical significance on the primary endpoint (relapse-free survival), and the Independent Data Monitoring Committee recommended discontinuing the KEYNOTE-630 study on the basis that its effect was not significant.

Although the pre-analysis data was negative for Keytruda, Merck noted that overall survival has not been formally evaluated. The safety profile of Keytruda in the KEYNOTE-630 study was consistent with previous findings. The company has notified the researchers to stop the study and advised patients participating in the study to negotiate alternative treatment options with their healthcare providers. Merck will continue to analyze data from both trials and plans to share the findings with regulators and the scientific community.

Cancer treatment is an important strategic direction for Merck, and Keytruda has been successfully or approved for marketing in several cancer types, including lung, kidney, skin, breast, cervical, bladder and other cancers. Merck currently has more than 30 Phase 3 clinical studies in early stage cancer, covering 10 cancer species. The termination of the KEYNOTE-867 and KEYNOTE-630 studies are two of them. In August, Merck also had to terminate a Phase 3 study that was evaluating the efficacy of the PD-1 inhibitor Keytruda in combination with the anti-Tigit antibody vibostolimab and chemotherapy as a first-line treatment for extensive small-cell lung cancer. At the time, the Data Monitoring Board found that the overall survival data for Keytruda in this indication was invalid. At the same time, safety concerns also emerged, with patients receiving the combination regimen showing a higher incidence of toxicity, including some immune-related toxicities.

In May, Merck terminated another Phase 3 trial of a combination of Keytruda and vibostolimab in resected high-risk melanoma patients. That same month, Merck announced that Keytruda failed to meet expectations in a Phase 3 study of endometrial cancer. In patients with newly diagnosed high-risk endometrial cancer, PD-1 blockers did not significantly improve disease-free survival compared with placebo as chemotherapy adjunctive treatment, with or without radiotherapy.