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Page 58 Bhasin et al. J Transl Genet Genom 2024;8:55-76 https://dx.doi.org/10.20517/jtgg.2023.46

(24) HR 0.85 (CI 0.72-1, P = 0.053)
Grade 3/4 TRAE 26% ipilimumab patients vs. 3% placebo patients
NCT02601014 II mCRPC expressing AR- 30 Ipilimumab + nivolumab PSA response Cohort 1:
(25) V7 - PSA response 13%
- ORR 25%
- Median PFS 3 months (95%CI: 2.1-NR)
- Median OS 8.2 months (95%CI: 5.5-10.4)
Cohort 2:
- PSA response 0%
- ORR 0%
- Median PFS 2.7 months (95%CI: 2.1-5.9)
- Median OS 14.2 months (95%CI: 8.5-NA)
- Grade 3/4 TRAE 46% in cohort 1, 53% in cohort 2

mCRPC: Metastatic castrate-resistant prostate cancer; ORR: overall response rate; OS: overall survival; PFS: progression-free survival; PSA 50: 50% reduction in PSA; TRAE: treatment-related adverse events; HR:
hazard ratio.

Alternatively, durvalumab was studied in combination with olaparib. Landmark 12-month progression-free survival (PFS) was noted in 51.5%
(95%CI: 25.7%-72.3%) of patients enrolled . Lastly, durvalumab combined with and without tremelimumab, a cytotoxic T-lymphocyte associated protein 4
[18]
(CTLA-4) inhibitor, was evaluated in patients with metastatic castrate-resistant prostate cancer who had progressed on prior androgen receptor targeting
therapy and/or one line of taxane-based therapy. The primary endpoint of this study, ORR, was 0% (95%CI: 0%-25%) in the durvalumab monotherapy group
[19]
and 16% (95%CI: 6%-32%) in the combination therapy arm .

Cytotoxic T-lymphocyte associated protein 4
Ipilimumab was studied alone and in combination with nivolumab in patients with prostate cancer. Ipilimumab monotherapy was evaluated vs. placebo in

asymptomatic or minimally symptomatic chemotherapy-naïve patients with metastatic castrate-resistant prostate cancer; the evaluation did not provide any
evidence of survival advantage with ipilimumab over placebo. In fact, phase III trial testing demonstrated no apparent overall survival benefit with the use of
ipilimumab, the median OS of 28.7 months with ipilimumab (95%CI: 24.5-32.5 months) vs. placebo which had a median OS of 29.7 months
(95%CI: 26.1-34.2 months) . Another trial examined ipilimumab vs. placebo following radiation in patients with metastatic castrate-resistant prostate cancer
[23]
and did not demonstrate any efficacy signal favoring the use of ipilimumab. Median OS was 11.1 months (95%CI: 9.5-12.7) with the use of ipilimumab vs. 10
[24]
months (95%CI: 8.3-11) with placebo . When studied in combination, ipilimumab/nivolumab showed limited therapeutic efficacy with only 13.3%
(95%CI: 2.5%-39.1%) of patients experiencing PSA50. Additionally, 53% of patients experienced a grade 3-4 adverse event and 47% experienced grade 3-4
immune-related adverse events including colitis, adrenal insufficiency, and hypophysitis, among others.

Ultimately, ipilimumab/nivolumab in metastatic castrate-resistant prostate cancer was deemed to have a significant risk of adverse events with minimal
response .
[25]