TY - JOUR
T1 - Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial
AU - Nguyen, Charles B.
AU - Reimers, Melissa A.
AU - Perera, Chamila
AU - Abida, Wassim
AU - Chou, Jonathan
AU - Feng, Felix Y.
AU - Antonarakis, Emmanuel S.
AU - McKay, Rana R.
AU - Pachynski, Russell K.
AU - Zhang, Jingsong
AU - Reichert, Zachery R.
AU - Palmbos, Phillip L.
AU - Caram, Megan E.V.
AU - Vaishampayan, Ulka N.
AU - Heath, Elisabeth I.
AU - Hopkins, Alexander C.
AU - Cieslik, Marcin P.
AU - Wu, Yi Mi
AU - Robinson, Dan R.
AU - Baladandayuthapani, Veerabhadran
AU - Chinnaiyan, Arul M.
AU - Alva, Ajjai S.
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research.
PY - 2024/8/1
Y1 - 2024/8/1
N2 - 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 in patients with CDK12-altered mCRPC. Patients and Methods: 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 four cycles, followed by nivolumab 480 mg every 4 weeks. Cohort C received nivolumab alone 480 mg every 4 weeks. Patients with CDK12-altered nonprostate tumors were enrolled in cohort B and not reported. The primary endpoint was a 50% reduction in PSA (PSA50). Key secondary endpoints included PSA progression-free survival, overall survival, objective response rate, and safety. Results: PSA was evaluable in 23 patients in cohort A and 14 in cohort C. Median lines of prior therapy were two 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% confidence interval (CI), 1%–28%] in cohort A with two responders; neither had microsatellite instability or a tumor mutational burden >10 mutations/megabase. No PSA50 responses occurred in cohort C. Median PSA progression-free survival 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 overall survival 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. Conclusions: There was minimal activity with ICI therapy in patients with CDK12-altered mCRPC.
AB - 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 in patients with CDK12-altered mCRPC. Patients and Methods: 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 four cycles, followed by nivolumab 480 mg every 4 weeks. Cohort C received nivolumab alone 480 mg every 4 weeks. Patients with CDK12-altered nonprostate tumors were enrolled in cohort B and not reported. The primary endpoint was a 50% reduction in PSA (PSA50). Key secondary endpoints included PSA progression-free survival, overall survival, objective response rate, and safety. Results: PSA was evaluable in 23 patients in cohort A and 14 in cohort C. Median lines of prior therapy were two 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% confidence interval (CI), 1%–28%] in cohort A with two responders; neither had microsatellite instability or a tumor mutational burden >10 mutations/megabase. No PSA50 responses occurred in cohort C. Median PSA progression-free survival 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 overall survival 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. Conclusions: There was minimal activity with ICI therapy in patients with CDK12-altered mCRPC.
UR - http://www.scopus.com/inward/record.url?scp=85200424044&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-24-0400
DO - 10.1158/1078-0432.CCR-24-0400
M3 - Article
C2 - 38787530
AN - SCOPUS:85200424044
SN - 1078-0432
VL - 30
SP - 3200
EP - 3210
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -