Merck’s Keytruda Secures Back-to-Back Phase III Wins in Renal Cell Carcinoma and Muscle-Invasive Urothelial Carcinoma

Rahway, New Jersey – Merck’s blockbuster PD-1 inhibitor Keytruda (pembrolizumab) improved overall survival when used as an adjuvant treatment for renal cell carcinoma patients who are at intermediate-high or high risk of recurrence after nephrectomy, according to results of the Phase III KEYNOTE-564 trial posted Saturday.

Compared with placebo, patients in the Keytruda arm saw a 38% drop in the risk of death. The effect was statistically significant with a p-value of 0.002, according to Merck’s announcement. Keytruda-treated patients had an overall survival (OS) rate of 91.2% at 48 months versus 86% in placebo counterparts.

KEYNOTE-564 is a randomized and double-blinded trial that enrolled 994 renal cell carcinoma (RCC) patients who had undergone nephrectomy but were still at intermediate-high or high risk of recurrence. In June 2021, Merck posted 24-month follow-up data from the trial showing that Keytruda met its primary endpoint by cutting the risk of disease recurrence or death by 32% compared with placebo.

OS is a key secondary endpoint of KEYNOTE-564.

“This is the second KEYTRUDA study to demonstrate a significant overall survival benefit in an earlier stage of cancer, and these new results add to the progress we’re making in earlier stages of disease,” Marjorie Green, head of oncology, global clinical development at Merck Research Laboratories, said in a statement.

On Friday, Merck also announced an adjuvant-setting victory for Keytruda in the Phase III KEYNOTE-123 trial, in which the immunotherapy significantly improved disease-free survival (DFS) in patients with localized muscle-invasive urothelial carcinoma (MIUC).

At 22.3 months of follow-up, Keytruda reduced the risk of disease recurrence or death by 31% compared to plain observation in MIUC patients who had undergone surgery. Median DFS was 29 months in the Keytruda arm versus 14 months in the observation group. Keytruda’s DFS benefits were consistent regardless of PD-1 expression status.

KEYNOTE-123 is also assessing OS as one of its dual primary endpoints but at the time of the interim analysis data were immature. The trial will continue to follow the patients as their survival data mature.

Merck presented the findings from both KEYNOTE-564 and KEYNOTE-123 at an oral session at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium, held in San Francisco at the end of January.

The company will continue to investigate Keytruda in both cancers, for which it has sweeping clinical development programs. In RCC, the pharma is also assessing the PD-1 blocker with its own HIF-2α inhibitor Welireg (belzutifan) or with Eisai’s VEGF tyrosine-kinase inhibitor Lenvima (lenvatinib). In MIUC, Merck is partnered with Pfizer’s Seagen and Astellas to assess Keytruda in several Phase III trials, including KEYNOTE-866, KEYNOTE-B15 and KEYNOTE-905.