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Table 2 Clinical trials for checkpoint inhibitors alone and compared to standard care of treatment

From: T cell exhaustion: from pathophysiological basics to tumor immunotherapy

Agent (inhibited checkpoint) Setting Phase Treatment Tumor response OS (PFS) in MO Toxicity (irAE grade ≥3) Ref
Ipilimumab (CTLA-4) Advanced uveal melanoma II Ipilimumap SD 47% 6.8 (2.8) Colitis, diarrhea, elevated liver enzymes [176]
After complete resection of advanced melanoma III Ipilimumab or placebo after complete resection NM (26.7 vs 17.1) Diarrhea, colitis,rash, pruritus, hypo-physitis, elevated liver enzymes [170]
Advanced melanoma II Ipilimumap CR 0% PR 10%
SD 10%
PD 65%
8.7 (2.7) Elevated liver enzymes [205]
Relapse of malignancy after allogeneic hematopoietic stemcell transplan-tation I Ipilimumab ORR 6.9%
CR 6.9%
PR 3.4%
24.7 Arthritis, pneumonitis [175]
Relapsed and refractory B-cell NHL I Ipilimumap NM NM Diarrhea, fatigue, [206]
Treme-limumap (CTLA-4) Advanced melanoma III Tremeli-mumab vs. standard-of-care chemotherapy NM 12.6 vs 10.7 (at 6 MO 20.3%vs 18.1%) Diarrhea, colitis,
pruritus, rash
[183]
Advanced melanoma I Anti-CD40 + Tremeli-mumab NM 26.1 (2.5) Diarrhea, colitis, pruritus, rash [212]
Advanced gastric and esophageal adeno-carcinoma II Tremeli-mumap PR 5.6%
SD 22%
4.8 (2.8) Diarrhea, atrial fibrillation, increased liver enzymes [177]
Advanced (metastatic) colorectal carcinoma II Tremeli-mumap PR 2.2% PD 95.6% At 1a 4.8 vs 10.7% (at 6 MO 2.3 vs 2.1%) Diarrhea, fatigue, colitis [185]
Advanced NSCLC II Tremeli-mumap vs. best supportive care PR 4.8%
SD 16.6%
20.9% (34%) at 3 MO Diarrhea, colitis [213]
HHC and chronic hepatitis C II Tremeli-mumap SD 58.8%
PR 17.6%
8.2 (6.5) Skin rash, diarrhea, syncope, diverticulitis, depression [179]
Advanced malignant mesothelioma II Tremeli-mumap PR 3%
SD 38%
11.3 Gastrointes-tinal events, dermatologi-cal events, fever [214]
Nivolumab (PD-1) Advanced refractory squamous NSCLC II Nivolumab 3 mg/kg every 2 weeks until progression PR 14.5%
SD 26%
PD 44%
8.2 (1.9); 1a 40.1% Fatigue, diarrhea, rash pruritus [196]
Untreated melanoma (BRAF wild type vs mutated) I Nivolumab + Ipilimumab vs Ipilimumab + placebo WT [BRAF+]
ORR 61% vs 11% [3% vs 1%] CR 16% vs 0%
[5% vs 0%] PR 28% vs 4%
[7% vs 1%] SD 9% vs 13% [5% vs 7%]
NM Diarrhea rash. fatigue pruritus, elevated liver enzymes [187]
Untreated melanoma without BRAF mutation III Nivolumab vs Dacarbazine ORR 40,0% vs 13,9% 72.9% vs 42.1% at 1a (5.1 vs 2.2) Fatigue, pruritus, nausea, diarrhea [186]
Advanced Squamous-Cell NSCLC III Nivolumab vs Docetaxel ORR 20 vs 9%
CR 1 vs 0%
PR 26 vs 12%
SD 39 vs 47%
PD 56% vs 48%
9.2 vs 6.0 (3.5 vs 2.8) Fatigue, leukopenia [191]
Advanced non-Squamous-Cell NSCLC III Nivolumab vs Docetaxel ORR 19% vs 12% CR 4 vs 1%
PR 52% vs 35%
SD 12;7% vs 21% PD 22.2% vs 14.6%
12.2 vs 9.4 (2.3 vs 4.2) Fatigue, nausea, diarrhea [192]
Relapsed or refractory Hodgkin 's lymphoma I Nivolumab CR 17%
PR 70%
SD 13%
NM Leukopenia, stomatitis increased lipase levels, pancreatitis [206]
Pretreated advanced NSCLC (s and ns) I Nivolumab ORR 17.1% (16.7% s vs 17.6% ns) 9.9 Rash, Colitis [190]
Untreated melanoma III Nivolumab vs Nivolumab + Ipilimumab vs Ipilimumab ORR 14.6% vs 19.2% vs 6.3%
CR 8.9% vs 11.5% vs 2.2%
PR 34.8% vs 46.2% vs 16.8% SD 10.8% vs 13.1% vs 21.9% PD 37.7% vs 22.6% vs 48.9%
11.5 vs 2.9 vs 6.9 Diarrhea, fatigue, pruritus, rash [188]
Platinum resistant ovarian cancer II Ipilimumab CR 10% PR 5%
SD 30%
PD 50%
20 (3.5) Lympho-cytopenia, anemia [215]
Advanced melanoma after anti CTLA-4 treatment III Nivolumab vs investigators choice of chemo ORR 31.7% vs 10.6%
CR 3.3% vs 0% PR 28.3% vs 10.6%
SD 23.3% vs 34%
PD 35% vs 31.9%
(4.7 vs 4.2) Anemia, fatigue, vomitting [189]
Advanced renal cell carcinoma III Nivolumab vs Everolimus ORR 25% vs 5% CR 1% vs <1% 25.0 vs 19.6 (4.6 vs 4.4) Fatigue, diarrhea, rash [216]
Pembroli-zumab (PD-1) Advanced NSCLC I Pembroli-zumab ORR 19.4% 12.0 (3.7) Fatigue, rash, diarrhea [217]
Advanced triple negative breast cancer Ib Pembroli-zumab ORR 18.5% CR 3.7%; PR 14.8% SD 25.9% PD 48.1% NM Anemia, headache, [218]
Previously treated advanced non-small-cell lung cancer II/III Pembroli-zumab vs Docetaxel NM 10.4 vs 12.7 vs 8.5 (3.9 vs 4.0 vs 4.0) Anemia, headache, [193]
Advanced melanoma I Pembroli-zumab ORR 38.6% vs 28.6% 23 (4) Anemia, headache, [194]
Progressive metastatic carcinoma with or without mismatch repair-deficiency II Pembroli-zumab ORR 40% vs 78% for mismatch repair-deficienct CRC and 0% vs 11% mismatch repair-proficient colorectal cancer NM Lympho-penia, anemia, diarrhea, bowel obstruction, elevated liver enzymes [195]
Advanced melanoma III Pembrolizumab vs Ipilimumab ORR 89.4% vs 96.7% vs 87.9% At 1a 74.1% vs 68.4% (at 6 MO 47.3%vs 46.4% vs 26.5%) Lympho-penia, anemia, diarrhea, bowel obstruction, elevated liver enzymes [219]
Atezoli-zumab (PD-L1) Previously treated metastatic uorthelial carcinoma II Atezoli-zumab ORR 15% CR 5% PR 10% SD 19% PD 51% NM Fatigue, decreased appetite, dyspnoea, anemia, colitis [202]
Previously treated NSCLC II Atezo-lizumab vs Docetaxel NM 12.6 vs 9.7 Diarrhea, asthenia, neutropenia [201]
  1. Abbreviations: CR complete response, HCC hepatocellular carcinoma, irAE immune related adverse effects, MO months, NM not mentioned, NSCLC non small cell lung cancer, ORR overall response rate, OS overall survival, PD progressive disease, PFS progression free survival, PR partial response, SD stable disease