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