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 in patients with CDK12-altered mCRPC.
Eligible patients had mCRPC with deleterious CDK12 alterations and any prior therapies except ICI. Cohort A received ipilimumab (1 mg/kg) with nivolumab (3 mg/kg) every 3 weeks for up to 4 cycles, followed by nivolumab 480 mg every 4 weeks. Cohort C received nivolumab alone 480 mg every 4 weeks. Patients with CDK12-altered non-prostate tumors were enrolled in cohort B and not reported. The primary endpoint was 50% reduction in PSA (PSA50). Key secondary endpoints included PSA progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety.
PSA was evaluable in 23 patients in cohort A and 14 in cohort C. Median lines of prior therapy were 2 in cohorts A and C, including any prior novel hormonal agent (74% and 79%) and chemotherapy (57% and 36%). The PSA50 rate was 9% (95% CI 1-28%) in cohort A with 2 responders; neither had microsatellite instability or a tumor mutational burden ≥10 mutations/megabase. No PSA50 responses occurred in cohort C. Median PSA-PFS was 7.0 months (95% CI 3.6-11.4) in cohort A and 4.5 months (95% CI 3.4-13.8) in cohort C. Median OS was 9.0 months (95% CI 6.2-12.3) in cohort A and 13.8 months (95% CI 3.6-not reached) in cohort C.
There was minimal activity with ICI therapy in patients with CDK12-altered mCRPC.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2024 May 24 [Epub ahead of print]
Charles B Nguyen, Melissa A Reimers, Chamila Perera, Wassim Abida, Jonathan Chou, Felix Y Feng, Emmanuel S Antonarakis, 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 Robinson, Veerabhadran Baladandayuthapani, Arul M Chinnaiyan, Ajjai S Alva
University of Michigan-Ann Arbor, Ann Arbor, MI, United States., Moffitt Cancer Center, St. Louis, MO, United States., Memorial Sloan Kettering Cancer Center, New York, NY, United States., University of California, San Francisco, San Francisco, CA, United States., University of Minnesota, Minneapolis, United States., University of California, San Diego, La Jolla, CA, United States., Washington University School of Medicine, St. Louis, United States., Moffitt Cancer Center, Tampa, Florida, United States., University of Michigan-Ann Arbor, Ann Arbor, Mi, United States., University of Michigan-Ann Arbor, Ann Arbor, Michigan, United States., University of Michigan Medical School, Ann Arbor, Michigan, United States., Karmanos Cancer Center, Detroit, MI, United States., University of Michigan Medical School, Ann Arbor, MI, United States., University of Michigan-Ann Arbor, ann arbor, michigan, United States., University of Michigan-Ann Arbor, Ann Arbor, United States.