# KEYNOTE-641

Source: https://onco.cc/trials/keynote-641/  
OnCo record `keynote-641` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding pembrolizumab to enzalutamide did not help. The trial was stopped for futility, and three times as many men had a serious side effect.

## Summary

KEYNOTE-641 randomised 1,244 men with chemotherapy-naive metastatic castration-resistant prostate cancer to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles, both with enzalutamide 160 mg daily.

At the data cutoff of 12 December 2022, median follow-up 27.6 months, neither primary endpoint was met. Median overall survival was 24.7 months with pembrolizumab against 27.3 months with placebo, hazard ratio 1.04 (95 percent confidence interval 0.88 to 1.22, p=0.66). Median radiographic progression-free survival was 10.4 against 9.0 months, hazard ratio 0.98 (0.84 to 1.14, p=0.41). The prespecified futility boundary for overall survival was crossed and the study was stopped.

The toxicity difference is the reason this is a harm and not merely a null result. Grade 3 or higher treatment-related adverse events occurred in 192 of 615 participants (31.2 percent) on pembrolizumab with enzalutamide against 67 of 620 (10.8 percent) on placebo with enzalutamide, and 71 (11.5 percent) against 21 (3.4 percent) discontinued for a treatment-related adverse event.

## Fields

- Kind: Trial
- Status: negative
- Last checked: 2026-09-25
- Also known as: KEYNOTE-641; MK-3475-641
- Registry id: NCT03834493
- Phase: 3
- Setting: Chemotherapy-naive metastatic castration-resistant prostate cancer, prior abiraterone permitted and prior docetaxel allowed only in the hormone-sensitive setting: pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles with enzalutamide 160 mg daily, with dual primary endpoints of overall survival and radiographic progression-free survival
- Sponsor: Merck Sharp & Dohme
- Enrolled: 1244
- Result: Median overall survival 24.7 against 27.3 months (hazard ratio 1.04, 95 percent confidence interval 0.88 to 1.22) and radiographic progression-free survival 10.4 against 9.0 months (0.98, 0.84 to 1.14); stopped for futility. Grade 3 or higher treatment-related adverse events 31.2 against 10.8 percent.
- Outcomes: Overall survival (median): Pembrolizumab with enzalutamide 24.7 months vs Placebo with enzalutamide 27.3 months, HR 1.04; Grade 3 or higher treatment-related adverse events: Pembrolizumab with enzalutamide 31.2% vs Placebo with enzalutamide 10.8%
- Replication: IMbassador250 found the same for atezolizumab with enzalutamide in 759 men (hazard ratio 1.12).

## Sources

- ClinicalTrials.gov NCT03834493: https://clinicaltrials.gov/study/NCT03834493
- KEYNOTE-641 (Annals of Oncology 2025): https://doi.org/10.1016/j.annonc.2025.05.007

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Androgen receptor pathway inhibitor (ARPI)](https://onco.cc/terms/arpi/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Prostate cancer programmes that failed, and what each failure taught](https://onco.cc/terms/prostate-failed-programmes/)
- trials: [IMbassador250](https://onco.cc/trials/imbassador250/), [KEYNOTE-921](https://onco.cc/trials/keynote-921/), [KEYNOTE-991](https://onco.cc/trials/keynote-991/)

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