Table 3.
Combination strategies and targets with ICIs in mCRPC.
| Trial/NCT | Phase | Patient Population | Treatment | Primary Endpoint | Results |
|---|---|---|---|---|---|
| ICIs + cytokines | |||||
| SWOG S0354 (NCT00433446) | II | mCRPC patients with prior taxane therapy | Siltuximab every 2 weeks for 12 cycles | PSA RR defined as 50% reduction | Overall PSA RR of 3.8% (95% CI: 0.5%, 13.0%) |
| ICIs + cancer vaccines | |||||
| NCT03024216 | 1b | Asymptomatic or minimally symptomatic mCRPC patients | Atezolizumab followed by sipuleucel-T (Arm 1) or sipuleucel-T followed by atezolizumab (Arm 2) | Safety | At least one treatment-related AE was reported in 31 subjects (83.8%), including 7 (18.9%) with at least one grade 3 treatment-related AE |
| ICIs + PARP inhibitors | |||||
| KEYNOTE-365 (NCT02861573) Cohort A | 1b/II | Docetaxel-pretreated mCRPC patients who progressed within 6 months of screening and were molecularly unselected | Pembrolizumab + olaparib | Safety, PSA response rate, ORR | The confirmed PSA response rates in patients with a baseline PSA measurement were 15% (15/102) for the total population and 19% (11/59) for patients with RECIST-ORR was 8.5% (five PRs) in patients with RECIST-measurable disease. All 102 treated patients (100%) experienced at least one all-cause AE, and grade 3–5 AEs occurred in 74 patients (73%) Treatment-related AEs occurred in 93 patients (91%) |
| KEYLYNK-010 (NCT03834519) | III | mCRPC patients who progressed after chemotherapy and either abiraterone or enzalutamide | Pembrolizumab + olaparib vs. next-generation hormonal agent | OS, rPFS | rPFS (median 4.4 months with pembrolizumab + olaparib vs. 4.2 months with next-generation hormonal agent; HR 1.02, 95% CI 0.82–1.25; p = 0.55) and OS (15.8 mo vs. 14.6 mo; HR 0.94, 95% CI 0.77–1.14; p = 0.26) were not met. Study was stopped for futility. |
| NCT02484404 | II | mCRPC patients who had received prior enzalutamide and/or abiraterone unselected for somatic or germline mutations | Durvalumab + olaparib | rPFS, PSA response | 9 of 17 patients (53%) had a PSA decline of ≥50%. Median rPFS for all patients is 16.1 months (95% CI: 4.5–16.1 months) with a 12-month rPFS of 51.5% (95% CI: 25.7–72.3%) |
| ICIs + radioligand therapies | |||||
| PRINCE (NCT03658447) | 1b | mCRPC patients with high PSMA expression (SUVmax ≥20 in an index lesion, SUVmax >10 for all lesions ≥10 mm), and no FDG positive/PSMA negative lesions on paired baseline PET/CT | 177Lu-PSMA-617 + pembrolizumab | Safety, PSA response rate | PSA response rate was 76% (28/37 [95% CI 59–88]) and 7/10 (70%) patients with RECIST-measurable disease had a partial response |
| NCT02814669 | 1b | mCRPC patients with bone and lymph node and/or visceral metastases that progressed after androgen pathway inhibitor treatment | atezolizumab + radium-223 | Safety, ORR | All 44 patients had ≥1 all-cause AE; 23 (52.3%) had a grade 3/4 AE. 15 (34.1%) grade 3/4 and 3 (6.8%) grade 5 AEs were related to atezolizumab; none were related to radium-223. Confirmed ORR was 6.8% [95% CI, 1.4–18.7] |
| NCT05150236 | II | mCRPC patients with progression on prior androgen receptor pathway inhibitors, no more than one line of prior chemotherapy, significant PSMA avidity on 68GaPSMA-11 PET/CT (SUVmax ≥15 at one disease site and SUVmax ≥10 at measurable sites of disease. 10 mm), no FDG positive/PSMA negative disease and no contraindications to ICI | Ipilimumab + Nivolumab + 177Lu-PSMA-617 | 12-month PSA PFS | Ongoing |
Abbreviations: ADT androgen deprivation therapy; AEs adverse events; CI confidence interval; FDG [18] F-fluorodeoxyglucose; HR hazard ratio; ICIs immune checkpoint inhibitors; mCRPC metastatic castration-resistant prostate cancer; ORR objective response rate; OS overall survival; PD-L1 programmed death-1 ligand 1; PFS progression free survival; PR partial response; PSA prostate-specific antigen; PSMA prostate-specific membrane antigen; rPFS radiographic progression-free survival; RR response rate; SUVmax maximum standardized uptake value; TMB tumor mutational burden.