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Bhasin et al. J Transl Genet Genom 2024;8:55-76   https://dx.doi.org/10.20517/jtgg.2023.46                                                                                   Page 57


                              Table 1. Major immune checkpoint inhibitor trials & outcomes

                                                                            Patients
                              Trial ID         Phase Patients                             Drug                   Primary endpoint Outcome
                                                                            enrolled
                              NCT00730639      Ib     mCRPC                 17            Nivolumab              Safety tumor       Grade 3/4 TRAE 14%
                              (14)                                                                               response           ORR 0.0%
                                                                                                                 Pharmacokinetics
                              NCT01375842      I      mCRPC                 35            Atezolizumab           Safety activity    Grade 3/4 TRAE 11.4%
                              (15)                                                                                                  Confirmed PSA 50 8.6%
                                                                                                                                    Median OS 14.7 (95%CI: 5.9-NE) months
                              NCT03016312      III    mCRPC                 759           Atezolizumab +         Overall survival   Median OS 15.2 months (95%CI: 14-17) in atezolizumab + enzalutamide arm vs. OS 16.6
                              (16)                                                        enzalutamide                              (95%CI: 14.7-18.4) months in enzalutamide alone
                              NCT03170960      Ib     mCRPC                 132           Atezolizumab +         ORR                ORR 23%(95%CI: 17%-32%)
                              (17)                                                        cabozantinib                              Grade 3/4 TRAE 55%
                              NCT02484404      I/II   mCRPC                 17            Durvalumab + olaparib  Safety PFS         Grade 3/4 TRAE 12% 12-month PFS 51.5% (95%CI: 25.7%-72.3%)
                              (18)
                              NCT02788773      II     mCRPC                 52            Durvalumab +/-         ORR                ORR in durvalumab alone: 0% (95%CI: 0%-25%)
                              (19)                                                        tremelimumab                              ORR in durvalumab + tremelimumab: 16% (95%CI: 6%-32%)

                              NCT02787005      II     mCRPC                 258           Pembrolizumab          ORR                Cohort 1:
                              (20)                                                                                                      - ORR 5% (95%CI: 2%-11%)
                                                                                                                                        - Median OS 9.5 months
                                                                                                                                    Cohort 2:
                                                                                                                                        - ORR 3% (95%CI: < 1%-11%)
                                                                                                                                        - Median OS 7.9 months
                                                                                                                                    Cohort 3:
                                                                                                                                        - ORR < 1%
                                                                                                                                        - Median OS 14.1 months
                                                                                                                                        - Grade 3-5 TRAE 15%
                              NCT02787005      III    mCRPC                 126           Pembrolizumab +        ORR                Cohort 4:
                              (21)                                                        enzalutamide                                  - ORR 12.3% (95%CI: 6.1%-21.5%)
                                                                                                                                        - Median OS 17.6 months (95%CI: 14-22.6)
                                                                                                                                        - Grade 3/4 TRAE 27.2%
                                                                                                                                    Cohort 5:
                                                                                                                                        - ORR NA
                                                                                                                                        - Median OS 20.8 months (95%CI: 14.1-28.9)
                                                                                                                                    - Grade 3/4 TRAE 28.9%
                              NCT02861573      Ib/II  mCRPC                 104           Pembrolizumab +        Safety PSA response  PSA response 15%
                              (22)                                                        olaparib               ORR                ORR 8.5% (95%CI: 2.8%-19%)
                                                                                                                                    Median OS 14 months (95%CI: 10.4-18.2)
                                                                                                                                    Grade 3-5 TRAE 48%

                              NCT01057810      III    Chemotherapy naïve    837           Ipilimumab             Overall survival   Median OS 28.7 months (95%CI: 24.5-32.5) vs. placebo 29.7 months (95%CI: 26.1-34.2)
                              (23)                    mCRPC                                                                         Median PFS 5.6 months ipilimumab vs. 3.8 months placebo
                                                                                                                                    PSA response rate 23% ipilimumab vs. 8% placebo
                                                                                                                                    Grade 3/4 Immune-related TRAE 31% ipilimumab vs. 2% placebo
                              NCT00861614      III    mCRPC post radiation  998           Ipilimumab             Overall survival   Median OS 11.2 months (95%CI: 9.5-12.7) vs. 10 months (placebo) (95%CI: 8.3-11)
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