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Published on: March 6, 2018
Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12
Charles B Nguyen1, Melissa A Reimers2, Chamila Perera3
1Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
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.
Insights
Immune checkpoint inhibitor therapy showed minimal activity in patients with CDK12-altered metastatic castration-resistant prostate cancer (mCRPC). This phase 2 trial found limited efficacy for ipilimumab and nivolumab in this patient population.
Area of Science:
- Oncology
- Cancer Genetics
- Immunotherapy
Background:
- CDK12 inactivation is observed in metastatic castration-resistant prostate cancer (mCRPC).
- CDK12 alterations may influence response to immunotherapy.
- Evaluating immunotherapy in CDK12-altered mCRPC is crucial.
Purpose of the Study:
- To assess the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with mCRPC and CDK12 alterations.
- To determine response rates and survival outcomes in this specific patient group.
Main Methods:
- Phase 2 clinical trial enrolling patients with mCRPC and deleterious CDK12 alterations.
- Cohort A received ipilimumab plus nivolumab; Cohort C received nivolumab monotherapy.
- Primary endpoint was 50% prostate-specific antigen reduction (PSA50); secondary endpoints included survival and response rates.
Main Results:
- A 9% PSA50 rate was observed in Cohort A (ipilimumab + nivolumab), with two responders.
- No PSA50 responses were seen in Cohort C (nivolumab monotherapy).
- Median PSA progression-free survival was 7.0 months (Cohort A) and 4.5 months (Cohort C).
Conclusions:
- Immune checkpoint inhibitor therapy demonstrated minimal activity in patients with CDK12-altered mCRPC.
- Further research may be needed to identify predictive biomarkers or alternative treatment strategies.
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