Table 7 Landmark clinical trials in the development of CTLA-4 and PD-1/PD-L1 inhibitors
From: Clinical development of targeted and immune based anti-cancer therapies
CTLA-4 inhibitors | ||||||||||
 Ipilimumab (Yervoy®) | ||||||||||
  Drug Name | Clinical Trial ID | Trial Name | Population | Comparator | Year | Sponsor | Phase | N | Median OS (months) | Median PFS (months) |
CTLA-4 inhibitors | ||||||||||
 Ipilimumab (Yervoy®) | ||||||||||
  Ipilimumab (3 mg/kg/3w) | NCT00094653 | MDX010–020 | Melanoma | Gp100 vaccine | 2004–2011 | Bristol-Myers Squibb | III | 1783 | 10.0 vs 6.4 | 2.9 vs 2.8 |
  Ipilimumab (10 mg/kg/3w) | NCT00636168 |  | Melanoma | Placebo | 2008–2013 | Bristol-Myers Squibb | III | 1211 | 93.5 vs 87.7 | 63.5 vs 56.1 |
 Ipilimumab (3 mg/kg/3w) | NCT01696045 |  | Melanoma | None | 2012–2016 | Bristol-Myers Squibb | II | 14 | 18.2 | 2.6 |
  Ipilimumab (1 mg/kg/3w) + nivolumab | NCT02231749 | CHECKMATE-214 | RCC | Sunitinib | 2014–2017 | Bristol-Myers Squibb | III | 1390 | NA vs 26.0 | 11.6 vs 8.4 |
  Ipilimumab (1 mg/kg/3w) | NCT02060188 | CHECKMATE-142 | CRC | Chemotherapy | 2014–2018 | Bristol-Myers Squibb | II | 340 | NR | NR |
  Ipilimumab (1 mg/kg/ 6w) + nivolumab | NCT03083691 | BIOLUMA | NSCLC, SCLC | Nivolumab | 2017–2019 | Bristol-Myers Squibb | II | 106 | NR | NR |
  Ipilimumab (10 mg/kg/3mo) + bevacizumab | NCT00790010 |  | Melanoma | None | 2009–2018 | Bristol-Myers Squibb | I | 46 | NR | NR |
  Ipilimumab (10 mg/kg/3mo) | NCT01119508 |  | Melanoma | None | 2010–2016 | Bristol-Myers Squibb | II | 64 | NR | NR |
PD-1/PD-1 L inhibitors | ||||||||||
 Pembrolizumab (Keytruda®) | ||||||||||
  Pembrolizumab (2-10 mg/kg/3w) | NCT01295827 | KEYNOTE-001 | Melanoma, NSCLC | None | 2011–2018 | Merck Sharp & Dohme Corp. | I | 1260 | 12.0 | 3.7 |
  Pembrolizumab (2 mg/kg/3w) | NCT01704287 | KEYNOTE-002 | Melanoma | Chemotherapy | 2012–2015 | Merck Sharp & Dohme Corp. | II | 540 | 13.4 vs 11.0 | 2.9 vs 2.8 |
  Pembrolizumab (10 mg/kg/2w) | NCT01866319 | KEYNOTE-006 | Melanoma | Ipilimumab | 2013–2015 | Merck Sharp & Dohme Corp. | III | 834 | 74.1 vs 58.2% | 5.5 vs 2.8 |
  Pembrolizumab (10 mg/kg/2w) | NCT01848834 | KEYNOTE-012 | Head and Neck SCC | None | 2013–2016 | Merck Sharp & Dohme Corp. | I | 297 | 59% | 23% |
  Pembrolizumab (200 mg/3w) | NCT02142738 | KEYNOTE-024 | NSCLC | BSC | 2014–2016 | Merck Sharp & Dohme Corp. | III | 305 | 80.2 vs 72.4% | 62.1 vs 50.3% |
  Pembrolizumab (200 mg/3w) | NCT02453594 | KEYNOTE-087 | Hodgkin Lymphoma | None | 2015–2021 | Merck Sharp & Dohme Corp. | II | 211 | 97.5% | 63.4% |
  Pembrolizumab (200 mg/3w) + chemotherapy | NCT02039674 | KEYNOTE-021 | NSCLC | Chemotherapy | 2014–2016 | Merck Sharp & Dohme Corp. | I/II | 267 | NR | 13.0 vs 8.9 |
  Pembrolizumab (200 mg/3w) | NCT02335424 | KEYNOTE-052 | Urothelial cancer | None | 2015–2018 | Merck Sharp & Dohme Corp. | II | 374 | 67% | 30% |
  Pembrolizumab (10 mg/kg/2w) | NCT01876511 | KEYNOTE-016 | CRC (MSI) | None | 2013–2021 | Merck Sharp & Dohme Corp. | II | 171 | 76% | 64% |
  Pembrolizumab (200 mg/3w) | NCT02460198 | KEYNOTE-164 | CRC | None | 2015–2019 | Merck Sharp & Dohme Corp. | II | 124 | NR | NR |
  Pembrolizumab (10 mg/kg/2w) | NCT02054806 | KEYNOTE-028 | Solid tumors | None | 2014–2019 | Merck Sharp & Dohme Corp. | I | 477 | 62.6% | 20.8% |
  Pembrolizumab (200 mg/3w) | NCT02628067 | KEYNOTE-158 | Solid tumors | None | 2015–2023 | Merck Sharp & Dohme Corp. | II | 1350 | NR | NR |
  Pembrolizumab (200 mg/3w) | NCT02335411 | KEYNOTE-059 | Gastric and gastroesophageal junction adenocarcinomas | None | 2015–2019 | Merck Sharp & Dohme Corp. | II | 316 | 5.6 | 2.0 |
  Pembrolizumab (200 mg/3w) | NCT02576990 | KEYNOTE-170 | Large B-cell lymphoma | None | 2015–2019 | Merck Sharp & Dohme Corp. | II | 80 | NR | NR |
  Pembrolizumab (200 mg/3w) | NCT02578680 | KEYNOTE-189 | NSCLC | Placebo | 2016–2017 | Merck Sharp & Dohme Corp. | III | 646 | 69.2 vs 49.4% | 8.8 vs 4.9 |
 Nivolumab (Opdivo®) | ||||||||||
  Nivolumab (3 mg/kg/2w) | NCT01721746 | CHECKMATE-037 | Melanoma | Chemotherapy | 2012–2016 | Bristol-Myers Squibb | III | 631 | 15.7 vs 14.4 | 3.1 vs 3.7 |
  Nivolumab (3 mg/kg/2w) | NCT01642004 | CHECKMATE-017 | NSCLC | Docetaxel | 2012–2014 | Bristol-Myers Squibb | III | 352 | 9.2 vs 6.0 | 20.8 vs 6.4 |
  Nivolumab (3 mg/kg/2w) | NCT01673867 | CHECKMATE-057 | NSCLC | Docetaxel | 2012–2015 | Bristol-Myers Squibb | III | 792 | 12.2 vs 9.4 | 2.3 vs 4.2 |
  Nivolumab (3 mg/kg/2w) | NCT01668784 | CHECKMATE-025 | RCC | Everolimus | 2012–2015 | Bristol-Myers Squibb | III | 1068 | 25.0 vs 19.6 | 4.6 vs 4.4 |
  Nivolumab (3 mg/kg/2w) | NCT02181738 | CHECKMATE-205 | Hodgkin Lymphoma | None | 2014–2017 | Bristol-Myers Squibb | II | 338 | 98·7% | 10.0 |
  Nivolumab (3 mg/kg/2w) | NCT01592370 | CHECKMATE-039 | Hodgkin’s Lymphoma, | None | 2012–2020 | Bristol-Myers Squibb | I/II | 375 | NR | NR |
  Nivolumab (3 mg/kg/2w) | NCT02105636 | CHECKMATE-141 | Head and Neck SCC | Chemotherapy | 2014–2015 | Bristol-Myers Squibb | III | 506 | 36.0 vs 16.6 | NR |
  Nivolumab (3 mg/kg/2w) | NCT02387996 | CHECKMATE-275 | Advanced cancer | None | 2015–2016 | Bristol-Myers Squibb | II | 386 | 8.7 | 2.0 |
  Nivolumab (3 mg/kg/2w) | NCT02060188 | CHECKMATE-142 | CRC | None | 2014–2018 | Bristol-Myers Squibb | II | 340 | 73% | 14.3 |
  Nivolumab (3 mg/kg/2w) | NCT01928394 | CHECKMATE-032 | Advanced solid tumors | None | 2013–2018 | Bristol-Myers Squibb | I/II | 1150 | 9.7 | 16.2 |
  Nivolumab (3 mg/kg/2w) | NCT01658878 | CHECKMATE-040 | HCC | None | 2012–2019 | Bristol-Myers Squibb | I/II | 620 | 10.7 | 4.0 |
  Nivolumab (1 mg/kg/3w) + ipilimumab (3 mg/kg/3w) | NCT01844505 | CHECKMATE-067 | Melanoma | Ipilimumab + placebo | 2013–2016 | Bristol-Myers Squibb | III | 1296 | 63.8 vs 53.6% | 6.9 vs 2.9 |
 Atezolizumab (Tecentriq®) | ||||||||||
  Atezolizumab (1200 mg/3w) | NCT02108652 | IMVigor 210 | Urothelial cancer | None | 2014–2015 | Hoffmann-La Roche | II | 310 | 7.9 | 2.1 |
  Atezolizumab (1200 mg/3w) | NCT01903993 | POPLAR | NSCLC | Docetaxel | 2013–2015 | Hoffmann-La Roche | II | 287 | 12.6 vs 9.7 | 2.7 vs 3.4 |
  Atezolizumab (1200 mg/3w) | NCT02008227 | OAK | NSCLC | Docetaxel | 2014–2016 | Hoffmann-La Roche | III | 1225 | 13.8 vs 9.6 | 2.8 vs 4.0 |
 Durvalumab (Imfinzi®) | ||||||||||
  Durvalumab (10 mg/kg/2w) | NCT01693562 | Study 1108 | Advanced solid tumors | None | 2012–2019 | MedImmune LLC | I/II | 1022 | 1.5 | 18.2 |
  Durvalumab (10 mg/kg/2w) | NCT02516241 | DANUBE | Urothelial cancer | None | 2015–2019 | AstraZeneca | III | 1200 | NR | NR |
  Durvalumab (10 mg/kg/2w) | NCT02125461 | PACIFIC | NSCLC | Placebo | 2014–2017 | AstraZeneca | III | 713 | NR | 16.8 vs 5.6 |
 Avelumab (Bavencio®) | ||||||||||
  Avelumab (10 mg/kg/2w) | NCT02155647 | JAVELIN Merkel 200 | Merkel Cell Carcinoma | None | 2014–2019 | EMD Serono | II | 204 | 11.3 | 2.0 |
  Avelumab (10 mg/kg/2w) | NCT01772004 | JAVELIN Solid Tumor | Advanced solid tumors | None | 2013–2018 | EMD Serono | I | 1758 | 13.7 | 2.7 |