Combination anti-PD-1/PD-L1 and anti-CTLA-4 therapy trials
| Study name | Year, lead author | Tumor type | Line of therapy | Combination regimen | Patients (total n) | Biomarker selection | Primary endpoint | Trial design | Primary endpoint met | FDA-approved therapy | Strong biological rationale | New biomarker | Comparator arms of monotherapy | Clinically meaningful primary endpoint |
| Phase II trials | ||||||||||||||
| Alliance A091401 | 2018, D’Angelo | Sarcoma | 2+ | Nivolumab plus ipilimumab | 96 | Unselected | ORR (N and N+I)–non-comparative | N or N+I (1:1) | Yes | No | No | No | Yes | Yes |
| CONDOR | 2019, Siu | HNSCC | 2+ | Durvalumab plus tremelimumab | 267 | PD-L1 | ORR (D+T)–non-comparative | PD-L1<25%, D+T or D or T (2:1:1) | Yes | No | No | No | Yes | Yes |
| IFCT-1501 MAPS2 | 2019, Scherpereel | Mesothelioma | 2+ | Nivolumab plus ipilimumab | 125 | Unselected | DCR at 12 weeks (N and N+I)–non-comparative | N or N+I (1:1) | Yes | No | No | No | Yes | Yes |
| NCT02558894 | 2019, O’Reilly | Pancreatic | 2 | Durvalumab plus tremelimumab | 65 | Unselected | ORR (D+T and D)–lead-in safety study, with expansion pending efficacy signal, non-comparative | D+T or D (1:1) | No | No | No | No | Yes | Yes |
| CO.26 | 2020, Chen | Colorectal | 3+ | Durvalumab plus tremelimumab | 180 | Unselected | OS (D+T vs BSC) | D+T or BSC (2:1) | Yes | No | Limited | No | No | Yes |
| NRG GY003 | 2020, Zamarin | Ovarian | 2+ | Nivolumab plus ipilimumab | 100 | Unselected | ORR at 6 months (N vs N+I) | N or N+I (1:1) | Yes | No | Limited | No | Yes | Yes |
| Phase III trials | ||||||||||||||
| CheckMate 214 | 2018, Motzer | RCC | 1 | Nivolumab plus ipilimumab | 1096 | Unselected | Coprimary: OS, ORR and PFS (in intermediate or poor prognostic risk) | N+I or sunitinib (1:1) | Yes | Yes | No | No | Yes | Yes |
| CheckMate 227 | 2018, Hellmann | NSCLC | 1 | Nivolumab plus ipilimumab | 1739 | TMB | Coprimary: PFS (N+I vs chemo in TMB high) | PD-L1≥1%, N+I or N or chemo (1:1:1) PD-L1<1%, N+I or N+chemo or chemo (1:1:1) | No | Yes | No | Yes | Yes | Yes |
| CheckMate 227 | 2019, Hellmann | NSCLC | 1 | Nivolumab plus ipilimumab | 1739 | PD-L1 | Coprimary: OS (N+I vs chemo in PD-L1≥1%) | Yes | Yes | No | No | Yes | Yes | |
| MYSTIC | 2020, Rizvi | NSCLC | 1 | Durvalumab plus tremelimumab | 1118 | PD-L1 | Coprimary: OS (D vs chemo in PD-L1≥25%), PFS and OS (D+T vs chemo in PD-L1≥25%) | D or D+T or chemo (1:1:1) | No | No | No | No | Yes | Yes |
| ARCTIC | 2020, Planchard | NSCLC | 3+ | Durvalumab plus tremelimumab | 595 | PD-L1 | Coprimary: PFS and OS (D+T vs SOC in PD-L1<25%) | Study A: PD-L1≥25%, D or SOC (1:1); Study B: PD-L1<25%, D+T or SOC or D or T (3:2:2:1) | No | No | No | No | Yes | Yes |
BSC, best supportive care; Chemo, chemotherapy; D, durvalumab; DCR, disease control rate; HNSCC, head and neck squamous cell carcinoma; I, ipilimumab; N, nivolumab; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PD-L1, programmed death ligand 1; PFS, progression free survival; RCC, renal cell carcinoma; SOC, standard of care; T, tremelimumab; TMB, tumor mutation burden.