Table 4.
ICI clinical trials in prostate adenocarcinoma.
| ICI Agent | Trial (Phase) | Setting | Arms | N | ORR | Median PFS | PFS HR (95% CI) | Overall Survival | OS HR (95% CI) | OS in PD-L1 Positive | AE |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ipilimumab | CheckMate650 (2) NCT02985957 [121] |
mCRPC Cohort 1 (n = 45): progressed after >1 2nd gen hormone therapy, chemotherapy naïve |
Ipilimumab (3mg/kg) + Nivolumab for up to four doses then nivolumab monotherapy | 45 | 25% | 5.5 mo (3.5–7.1) | 19.0 mo (11.5-NE) | G3–4: 42.2% | |||
| Nivolumab | Cohort 2 (n = 45): progressed after chemotherapy | 45 | 10% | 3.8 mo (2.1–5.1) | 15.2 mo (6.4-NE) | G3–4: 53.3% | |||||
| Ipilimumab | CA184-095 (3) NCT01057810 [119] |
mCRPC Chemotherapy naïve Asymptomatic or minimally symptomatic Without visceral metastases |
Ipilimumab (10 mg/kg) | 400 | PSA Response * 23% (19–27%) |
5.6 mo | 28.7 mo (24.5–32.5) | G3–4: 15% | |||
| Placebo | 202 | 8% (5–13%) | 3.8 mo | HR: 0.67 (0.55–0.81) | 29.7 mo (26.1–34.2) | HR: 1.11; (0.88 to 1.39) p = 0.3667 | G3–4: 1% | ||||
| Ipilimumab | CA184-043 (3) NCT01057810 [117,118] |
mCRPC Post-docetaxel |
Ipilimumab (10 mg/kg) + Radiation Therapy | 399 | 11.2 mo (9.6–12.6) | G3–4: 58.7% | |||||
| Placebo + Radiation Therapy | 400 | 10.0 mo (8.4–11.2) | HR: 0.84 (0.72–0.98), p = 0.03 * at 2-year minimum follow up |
G3–4: 41% | |||||||
| Pembrolizumab | Keynote-199 (2) NCT02787005 [123] |
mCRPC Cohort 1: PD-L1 positive |
Pembrolizumab | 133 | 5% (2–11%) | 9.5 mo | G3–4: 15% | ||||
| Cohort 2: PD-L1 negative | 66 | 3% (<1–11%) | 7.9 mo | ||||||||
| Cohort 3: Bone-predominant | 59 | NE | 14.1 mo | ||||||||
| Atezolizumab | IMbassador250 (3) NCT03016312 [124] |
mCRPC Progressed on abiraterone and docetaxel |
Atezolizumab + enzalutamide | 379 | 15.2 mo (14.0–17.0) | G3–4: 28.3% | |||||
| Enzalutamide | 380 | 16.6 mo (14/7–18.4) | HR, 1.12 (0.91, 1.37), p = 0.28 | G3–4: 9.6% |
* PSA response = 50% decrease from baseline confirmed by a second PSA value >/= 6 weeks later.