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Table 5 Registration trials leading to the FDA approval of PD-1/PD-L1 inhibitors in head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid cancers

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-012 (phase Ib)/pembrolizumab HNSCC (n = 60) PD-L1 ≥ 1% and refractory to platinum chemotherapy Pembrolizumab 10 mg/kg every 2 weeks   Safety 45% with serious AEs, 17% with grade 3-4 AEs (most common transaminitis, hyponatremia, and rash)
ORR 18% (95% CI 8-32%)
42
CheckMate 141 (phase III)/nivolumab HNSCC (n = 361) Previously treated with platinum-based chemotherapy Nivolumab 3 mg/kg every 2 weeks ICC: either weekly cetuximab 250 mg/m2 after a loading dose of 400 mg/m2, weekly methotrexate 40-60 mg/m2, or weekly docetaxel 30-40 mg/m2 OS 7.5 mos vs. 5.1 mos (HR 0.70, 97.73% CI 0.51-0.96, p = 0.01) 43
KEYNOTE-087 (phase II)/pembrolizumab cHL (n = 210) Relapsed after ≥3 lines of therapy or refractory cHL Pembrolizumab 200 mg every 3 weeks   ORR 69.0% (95% CI 62.3-75.2%)
CR 22.4% (95% CI 16.9- 28.6%)
44
CheckMate 039 (phase I), CheckMate 205 (phase II)/nivolumab cHL (n = 80) Previously treated with ASCT or brentuximab Nivolumab 3 mg/kg every 2 weeks   ORR 66.3% (95% CI 54.8-76.4) 45, 46
Five phase I and II trials (including KEYNOTE-164 and KEYNOTE-158)/pembrolizumab MSI-H or dMMR unresectable or metastatic solid tumors (n = 149 across five trials) Treatment-refractory to all standard therapies Pembrolizumab 200 mg every 3 weeks   ORR 39.6% 47-53
KEYNOTE-059 (phase II)/pembrolizumab Advanced gastric or gastroesophageal junction cancer (n = 259) PD-L1 ≥ 1% and progression on ≥2 lines of chemotherapy Pembrolizumab 200 mg every 3 weeks   ORR 11.2% (95% CI 7.6-15.7) 54
CheckMate 142 (phase II)/nivolumab Metastatic colorectal cancer (n = 74) Previously treated with fluoropyrimidine, oxaliplatin, and irinotecan Nivolumab 3 mg/kg every 2 weeks   ORR 31.1% (95% CI 20.8-42.9) 55
CheckMate 040 (phase 1/2) Advanced hepatocellular carcinoma (n = 262) Refractory to one previous line of therapy (including sorafenib), or intolerant of sorafenib Nivolumab 3 mg/kg every 2 weeks   Safety 12/48 patients (25%) grade 3-4 AEs with 3 (6%) having treatment-related serious AEs (pemphigoid, adrenal insufficiency, liver disorder)
ORR 20% (95% CI 15-26%)
56
JAVELIN Merkel 200 (phase II) Merkel cell carcinoma (n = 88) First-line and beyond Avelumab 10 mg/kg every 2 weeks   ORR 31.8% (95.9% CI 21.9-43.1) 57
  1. FDA Food and Drug Administration, PD-1 programmed cell death 1, PD-L1 programmed death ligand 1, HNSCC head and neck squamous cell carcinoma, AEs adverse events, ORR overall response rate, CI confidence interval, ICC investigator-choice chemotherapy, OS overall survival, HR hazard ratio, cHL classical Hodgkin lymphoma, CR complete response, ASCT autologous stem cell transplantation, MSI-H microsatellite instability-high, dMMR defective mismatch repair