KEYNOTE-991 - Adaptive Futility Boundary and Integrated Safety-Efficacy Monitoring in Immuno-Oncology
Year: 2026
Type: preprint
Abstract: KEYNOTE-991 was a Phase III trial of pembrolizumab plus enzalutamide in metastatic castration-resistant prostate cancer, discontinued at first interim analysis in March 2023 when both primary endpoints favored placebo. This document argues the failure was not biological but structural: the trial's monitoring architecture was calibrated for cytotoxic chemotherapy temporal logic, not immune checkpoint biology. The intervention rebuilds two operational documents; an adaptive DMC charter with immunotherapy-aware asymmetric futility boundaries, and an integrated safety-efficacy monitoring plan treating discontinuation as an efficacy-modifying variable rather than a tolerability endpoint. Anchored in ICH E6(R2), ICH E9(R1), and published irAE rechallenge literature.
Author: Koroma, Martha Wuya
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7161582845
Cites:
Cited by:
Related to: