Table 2.
Immune checkpoint inhibitor combination therapy evidence in mCRPC.
| Trail Name/NCT | Phase | Patient Population | Treatment | Primary Endpoint | Results |
|---|---|---|---|---|---|
| IMbassador250 (NCT03016312) | III | mCRPC patients who had progressed on abiraterone | Atezolizumab + enzalutamide vs. enzalutamide alone | OS | Stopped early due to low probability of trial achieving primary endpoint given risk of immune-mediated adverse events |
| KEYNOTE-641 (NCT03834493) | III | Chemo-naïve mCRPC patients who are abiraterone-naïve or are intolerant to or progressed on abiraterone | Pembrolizumab + enzalutamide vs. placebo + enzalutamide | OS, rPFS | Discontinued after an interim analysis showed no improvement in rPFS or OS |
| CheckMate 9KD (NCT03338790) | II | Chemo-naïve mCRPC patients with ongoing ADT and ≤2 prior novel hormonal therapies | Nivolumab and docetaxel with prednisone and then nivolumab | ORR, PSA response rate | Confirmed ORR (95% CI) was 40.0% (25.7–55.7), and the confirmed PSA50-RR (95% CI) was 46.9% (35.7–58.3) |
| CheckMate 7DX (NCT04100018) | III | Chemo-naïve mCRPC patients with ongoing ADT and ≤2 prior novel hormonal therapies | Nivolumab + docetaxel vs. placebo + docetaxel | rPFS, OS | Pending |
| KEYNOTE-365 (NCT02861573) Cohort B | 1b/II | Chemo-naïve mCRPC patients who progressed on 4 weeks or more of abiraterone or enzalutamide | Pembrolizumab + docetaxel + prednisone | Safety, PSA response rate, ORR | Confirmed PSA response rate was 34% and the confirmed ORR was 23%. TRAEs occurred in 100 patients (96%). Grade 3–5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis) |
| KEYNOTE-921 (NCT03834506) | III | Chemo-naïve mCRPC patients who progressed on 4 weeks or more of abiraterone or enzalutamide | Pembrolizumab + docetaxel vs. docetaxel alone |
OS, rPFS | Results presented at ASCO GU 2023 Conference: rPFS (median 8.6 mo with pembrolizumab + docetaxel vs. 8.3 mo with placebo + docetaxel; HR 0.85, 95% CI 0.7121.01; p = 0.0335) and OS (median 19.6 months vs. 19.0 months; HR 0.92, 95% CI 0.7821.09; p = 0.1677) were not met |
| CheckMate 650 (NCT02985957) | II | Asymptomatic/minimally symptomatic patients who progressed after 2nd-generation hormone therapy and have not received chemotherapy for mCRPC (cohort 1) and patients who progressed after taxane-based chemotherapy (cohort 2) | Ipilimumab + nivolumab | ORR; rPFS | Median rPFS (95% CI) in all treated patients was 5.5 (3.5–7.1) and 3.8 months (2.1–5.1) in cohorts 1 and 2. In patients with TMB above vs. below the median, the ORR was 50.0% (95% CI 26.0–74.0) vs. 5.3% (95% CI 0.1–26.0) |
| CheckMate 650 (NCT02985957) additional results | II | mCRPC patients previously treated with docetaxel | Nivolumab + ipilimumab q3weeks for 4 doses then nivolumab q4weeks (cohort 1) vs. nivolumab q3weeks for 8 doses and ipilimumab q6w for 4 doses then nivolumab q4weeks (cohort 2) vs. ipilimumab alone (cohort 3) vs. cabaziaxel (cohort 4) | ORR, PSA response rate, rPFS | ORR 9% (cohort 1) vs. 15% (cohort 2) vs. 4% (cohort 3) vs. 11% (cohort 4). PSA response rate 14% (cohort 1) vs. 18% (cohort 2) vs. 5% (cohort 3) vs. 24% (cohort 4) |
Abbreviations: ADT androgen deprivation therapy; CI confidence interval; HR hazard ratio; mCRPC metastatic castration-resistant prostate cancer; ORR objective response rate; OS overall survival; PD-L1 programmed death-1 ligand 1; PSA prostate-specific antigen; rPFS radiographic progression-free survival; RR response rate; TMB tumor mutational burden; TRAEs treatment-related adverse events.