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
| 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 |
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