Skip to main content

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
Back to article page