Merck's Keytruda (pembrolizumab) has encountered setbacks in two Phase 3 clinical trials, KEYNOTE-867 and KEYNOTE-630, evaluating its efficacy in combination with standard treatments for early-stage non-small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma (CSCC), respectively. The trials were halted prematurely following recommendations from independent data monitoring committees, which determined that the addition of Keytruda was unlikely to demonstrate a survival benefit. These failures pose a challenge to Merck's strategy to expand Keytruda's utility ahead of its anticipated patent expiration in 2028.
KEYNOTE-867: NSCLC Trial
The KEYNOTE-867 trial investigated Keytruda in combination with radiation therapy for patients with Stage III NSCLC who were ineligible for or declined surgery. An interim analysis revealed that the Keytruda combination did not significantly improve relapse, progression, or overall survival compared to radiation therapy plus placebo. Furthermore, the Keytruda arm exhibited a higher incidence of adverse events, including fatal outcomes, leading to the decision to terminate the study.
KEYNOTE-630: CSCC Trial
The KEYNOTE-630 trial assessed Keytruda as adjuvant therapy following surgery and radiation in patients with CSCC. The primary endpoint of recurrence-free survival was not met, as Keytruda did not demonstrate a statistically significant improvement compared to placebo in delaying cancer recurrence. Although overall survival data were not formally analyzed at this interim stage, preliminary indications did not favor Keytruda.
Implications for Keytruda's Expansion
Keytruda has become a blockbuster drug for Merck, generating $14 billion in sales in the first half of 2024 alone. While initial approvals were in melanoma and NSCLC, its expansion into new indications has recently faced challenges. These recent trial failures add to a series of setbacks, including three combination trial failures in late 2023 and two earlier in 2023 for lung and prostate cancer. These results highlight the complexities of cancer treatment and the challenges in demonstrating benefit with immunotherapy combinations in certain patient populations and disease stages.
