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Table 4 Registration trials leading to the FDA approval of PD-1/PD-L1 inhibitors in urothelial carcinoma and renal cell carcinoma

From: Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations

Study/Agent Tumor (n) Line of therapy Experimental arm Control arm Primary endpoint Ref.
KEYNOTE-052 (phase II)/pembrolizumab Urothelial carcinoma (n = 370) First-line cisplatin-ineligible Pembrolizumab 200 mg every 3 weeks   ORR 24% (95% CI 20-29) 32
KEYNOTE-045 (phase III)/pembrolizumab Urothelial carcinoma (n = 542) Refractory to platinum-based chemotherapy Pembrolizumab 200 mg every 3 weeks Paclitaxel 175 mg/m2 OR docetaxel 75 mg/m2 OR vinflunine 320 mg/m2 OS 10.3 mos vs. 7.4 mos (HR 0.73, 95% CI 0.59-0.91, p = 0.002)
PFS HR 0.98, 95% CI 0.81-1.19, p = 0.42
33
CheckMate 275 (phase II)/nivolumab Advanced urothelial carcinoma (n = 270) Previously treated with platinum-based chemotherapy Nivolumab 3 mg/kg every 2 weeks   ORR 28.4% (95% CI 18.9-39.5) for 81 patients with PD-L1 ≥ 5%, 23.8% (95% CI 16.5-32.3) for 122 PD-L1 ≥ 1%, and 16.1% (95% CI 10.5-23.1) for 143 with PD-L1 < 1% 34
IMVigor 210 (phase II)/atezolizumab Urothelial carcinoma (n = 315) Previously treated with platinum-based chemotherapy Atezolizumab 1200 mg every 3 weeks   ORR 27% (95% CI 19-37, p < 0.0001) for PD-L1 ≥ 5%, 18% (95% CI 13-24, p = 0.0004) for PD-L1 ≥ 1%, 15% (95% CI 11-20, p = 0.0058) for all patients compared to historical control 35
IMVigor 210 (phase II)/atezolizumab Urothelial carcinoma (n = 119) First-line cisplatin-ineligible Atezolizumab 1200 mg every 3 weeks   ORR 23% (95% CI 16-31) in total population 36
Study 1108 (phase II)/durvalumab Urothelial carcinoma (n = 191) Second-line Durvalumab 10 mg/kg every 2 weeks   ORR 17.8% (95% CI 12.7-24.0) in all patients, 27.6% (95% CI 19.0-37.5) for PD-L1 ≥ 25%, and 5.1% (95% CI 1.4-12.5) for PD-L1-negative 38
JAVELIN Solid Tumor (phase I)/avelumab Urothelial carcinoma (n = 249) Second-line Avelumab 10 mg/kg every 2 weeks   ORR 17.4% (95% CI 11.9-24.1, complete response in 6.2%) for 61 post-platinum patients ≥6 months of follow-up 40
CheckMate 025 (phase III)/nivolumab Advanced RCC (n = 821) Second-line Nivolumab 3 mg/kg every 2 weeks Everolimus 10 mg daily OS 25.0 mos vs. 19.6 mos (HR 0.73, 98.5% CI 0.57-0.93, p = 0.002) 41
  1. FDA Food and Drug Administration, PD-1 programmed cell death 1, PD-L1 programmed death ligand 1, ORR overall response rate, CI confidence interval, OS overall survival, HR hazard ratio, PFS progression-free survival, RCC renal cell carcinoma