Keytruda Achieves Phase III Success in Kidney and Bladder Cancer

Merck's renowned PD-1 inhibitor, Keytruda (pembrolizumab), has shown a significant improvement in the overall survival rate for patients with renal cell carcinoma (RCC) who are at an elevated risk of experiencing a recurrence post-nephrectomy, as per the Phase III KEYNOTE-564 clinical trial results. The treatment demonstrated a noteworthy 38% reduction in the risk of mortality, with a statistically significant p-value of 0.002. At the 48-month mark, the overall survival rate for those treated with Keytruda was 91.2%, outperforming the 86% rate observed in the placebo group.

The KEYNOTE-564 trial was a randomized, double-blind study involving 994 RCC patients who, despite undergoing nephrectomy, faced intermediate-high to high risk of recurrence. In June 2021, Merck reported 24-month follow-up data from the trial, indicating that Keytruda effectively reduced the risk of disease recurrence or death by 32% compared to the placebo group.

The overall survival (OS) metric is a crucial secondary endpoint in the KEYNOTE-564 trial. Marjorie Green, the head of oncology at Merck Research Laboratories, highlighted the significance of these findings, stating that this is the second study to show a substantial overall survival benefit for Keytruda in an earlier stage of cancer, marking a step forward in addressing the disease at earlier stages.

Additionally, Merck announced positive results for Keytruda in the Phase III KEYNOTE-123 trial, where the immunotherapy notably enhanced disease-free survival (DFS) in patients with localized muscle-invasive urothelial carcinoma (MIUC). The 22.3-month follow-up data revealed that Keytruda lowered the risk of disease recurrence or death by 31% when compared to simple observation. The median DFS for Keytruda-treated patients was 29 months, significantly longer than the 14 months observed in the observation group. Notably, the DFS benefits of Keytruda were consistent, irrespective of the PD-1 expression status.

The KEYNOTE-123 trial is also evaluating OS as one of its primary endpoints, but the data at the time of the interim analysis was not mature. The study will proceed with patient follow-up as the survival data becomes more established.

Merck presented the outcomes of both the KEYNOTE-564 and KEYNOTE-123 trials at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium, which took place over the weekend. The company is committed to further exploring Keytruda's potential in the treatment of both types of cancer, with extensive clinical development programs underway. In RCC, Merck is investigating the PD-1 inhibitor in combination with its HIF-2α inhibitor Welireg (belzutifan) or with Eisai’s VEGF tyrosine-kinase inhibitor Lenvima (lenvatinib). In the case of MIUC, Merck is collaborating with Pfizer’s Seagen and Astellas to evaluate Keytruda in several Phase III trials, including KEYNOTE-866, KEYNOTE-B15, and KEYNOTE-905.