The addition of pembrolizumab to enzalutamide and ADT did not extend survival or delay disease progression compared with enzalutamide and ADT alone.
The phase 3 KEYNOTE-641 trial (NCT03834493) exploring the combination of pembrolizumab (Keytruda), enzalutamide (Xtandi), and androgen deprivation therapy (ADT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been discontinued by Merck (MSD), the company announced in a press release.1
The discontinuation of the trial follows the recommendation of an independent Data Monitoring Committee, which reviewed findings from an interim analysis showing that the addition of pembrolizumab to enzalutamide and ADT did not improve the trial’s primary end points of overall survival (OS) and radiographic progression-free survival (rPFS) compared with enzalutamide and ADT alone.
Although overall toxicity was worse in the pembrolizumab arm, there were no new safety signals reported with any of the study drugs.
Overall, the double-blind phase 3 KEYNOTE-641 trial had enrolled 1240 patients with mCRPC who had not been treated with chemotherapy for mCRPC and who had either not received abiraterone acetate (Zytiga) or were intolerant to or progressed on the drug. Merck plans to share the data from the study at an upcoming conference.
“Throughout the clinical development of Keytruda, we have asked the tough questions in an effort to fully explore the potential of this breakthrough immunotherapy and determine how we could help as many patients as possible,” Eliav Barr, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, stated in the press release.1
“Science is rarely a straight line, and while we are disappointed in these study results, our research to investigate Keytruda in many difficult-to-treat types of cancer continues in earnest. We are extremely grateful to all the investigators and patients for their participation in these studies,” added Barr.
The KEYNOTE-641 results mark the second recent disappointment for pembrolizumab in prostate cancer. It was previously announced by Merck that the phase 3 KEYNOTE-991 trial (NCT04191096) exploring the combination of pembrolizumab, enzalutamide, and ADT in patients with metastatic hormone-sensitive prostate cancer has been stopped due to futility.2
Similar to KEYNOTE-641, the KEYNOTE-991 study was halted based on the recommendation of an independent Data Monitoring Committee. The panel had evaluated results of an interim analysis showing that adding pembrolizumab to enzalutamide and ADT did no improved OS or rPFS versus enzalutamide/ADT alone.
Pembrolizumab does not currently have an FDA-approved indication for patients with prostate cancer; however, the drug does have a tumor-agnostic approval for the treatment of patients with tumor mutational burden–high solid tumors.
1. Merck Provides Update on Phase 3 Trials KEYNOTE-641 and KEYNOTE-789. Published online February 28, 2023. Accessed February 28, 2023. https://www.merck.com/news/merck-provides-update-on-phase-3-trials-keynote-641-and-keynote-789/
2. Merck Announces KEYNOTE-991 Trial Evaluating KEYTRUDA® (pembrolizumab) Plus Enzalutamide and Androgen Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer to Stop for Futility. Published online January 25, 2023. Accessed January 26, 2023. https://bit.ly/3kN77Pf