Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial

• DOI: 10.1158/1078-0432.ccr-24-0400
• Publication Date: 2024-05-24T15:15:29Z
• Authors: Charles B. Nguyen; Melissa A. Reimers; Chamila Perera; Wassim Abida; Jonathan Chou; Felix Y. Feng; Emmanuel S. Anton...; Rana R. McKay; Russell K. Pachynski; Jingsong Zhang; Zachery R. Reichert; Phillip L. Palmbos; Megan E.V. Caram; Ulka N. Vaishampayan; Elisabeth I. Heath; Alexander C. Hopkins; Marcin P. Cieslik; Yi-Mi Wu; Dan R. Robinson; Veerabhadran Bala...; Arul M. Chinnaiyan; Ajjai S. Alva
• Keywords: Clinical endpoint; Enzalutamide

Abstract Purpose: CDK12 inactivation in metastatic castration-resistant prostate cancer (mCRPC) may predict immunotherapy responses. This phase 2 trial evaluated the efficacy of immune checkpoint inhibitor (ICI) therapy patients with CDK12-altered mCRPC. Patients and Methods: Eligible had mCRPC deleterious alterations any prior therapies except ICI. Cohort A received ipilimumab (1 mg/kg) nivolumab (3 every 3 weeks for up to four cycles, followed by 480 mg 4 weeks. C alone nonprostate tumors were enrolled cohort B not reported. The primary endpoint was a 50% reduction PSA (PSA50). Key secondary endpoints included progression-free survival, overall objective response rate, safety. Results: evaluable 23 14 C. Median lines two cohorts C, including novel hormonal agent (74% 79%) chemotherapy (57% 36%). PSA50 rate 9% [95% confidence interval (CI), 1%–28%] responders; neither microsatellite instability or tumor mutational burden >10 mutations/megabase. No responses occurred survival 7.0 months (95% CI, 3.6–11.4) 4.5 3.4–13.8) 9.0 6.2–12.3) 13.8 3.6–not reached) Conclusions: There minimal activity ICI