Table 1.

Phase I trial as well as approval stage characteristics of immune checkpoint inhibitors

CharacteristicIpilimumaba (36)Nivolumab (37)Pembrolizumab (24)Atezolizumab (25)Avelumab (38)Durvalumab (39)Ipilimumab + nivolumab (20)
Phase I stage
 Trial locationUSUSUSUS, EuropeUS, Europe, AsiaUS, Europe, AsiaUS
 Number of centers2112201044
 Tumor types1 (nonmetastatic melanoma)8 solid tumorsAll solid tumorsAll solid tumorsAll solid tumorsAll solid tumors1 (metastatic melanoma)
 Trial design (40)Preassigned dose levelsAccelerated titration design transitioned to a 3 + 3 design3 + 3 design3 + 3 design3 + 3 design3 + 3 design3 + 3 design
N, patients1920730171272786
N, dose levels3435467
 Response criteriaN/ARECIST 1.1 (10)RECIST 1.1 (10)RECIST 1.1 (10)RECIST 1.1 (10)Immune relatedModified WHO (41)
N, DLTs3000106
 MTD reachedYesNoNoNoNoNoYes
 Dose recommendation (parameter)Yes (toxicities)No clear dose recommendedYes (lowest dose with efficacy)Yes (PK)Yes (PK)Yes (PK/PD/safety data)Yes (toxicities)
Approval stage
 First FDA approvalMelanomaMelanomaMelanomaUrothelial carcinomaMerkel cell carcinoma (42)Urothelial carcinomaMelanoma
 Design of first pivotal trial leading to approvalPhase IIIPhase IIIPhase IbPhase IIPhase IIPhase IIPhase III
 Subsequent approvalsNo5 (NSCLC, kidney cancer, Hodgkin lymphoma, HNSCC, urothelial carcinoma)5 (NSCLC, HNSCC, Hodgkin lymphoma, urothelial carcinoma, MSI-H cancers)1 (NSCLC)1 (urothelial carcinoma)NoNo
 Response criteria pivotal trialsModified WHO (41)RECIST 1.1 (10) and International Working Group (Hodgkin; ref. 43)RECIST 1.1 (10) and revised response criteria for lymphomas (43)RECIST 1.1 (10)RECIST 1.1 (10)RECIST 1.1 (10)RECIST 1.1 (10)
 Selection biomarkerNoNoYes (PD-L1 expression is required for NSCLC indication) and MSI-H tested cancersNoNoNoNo
  • Abbreviations: HNSCC, head and neck small cell carcinoma; MSI-H, microsatellite instability-high; N/A, not applicable; NSCLC, non-small cell lung cancer; PD, pharmacodynamics; PK, pharmacokinetics; WHO, World Health Organization.

  • aThis phase I trial included patients with completely resected melanoma. Hence, response evaluation was not performed.