Table 1.
Therapy | Author, year, journal | Cancer type | Phase (no. of patients) | Findings, median PFS in months unless otherwise stated |
---|---|---|---|---|
Pembrolizumab versus ipilimumab | Robert, 2015, NEJM19 (KEYNOTE‐006) | Advanced melanoma | Phase 3 (834) | 5.5 (pembrolizumab every 2 weeks) versus 4.1 (pembrolizumab every 3 weeks) versus 2.8 (ipilimumab) |
Nivolumab with ipilimumab versus nivolumab or ipilimumab monotherapy | Larkin, 2015, NEJM20 | Untreated melanoma | Phase 3 (945) | 2.9 (ipilimumab) versus 6.9 (nivolumab) versus 11.5 (combination) |
Nivolumab plus ipilimumab versus ipilimumab monotherapy | Postow, 2015, NEJM21 | Untreated melanoma | Phase 2 (142) | Not reached (combination) versus 4.4 (ipilimumab) (BRAF‐WT tumors) |
Nivolumab plus ipilimumab, concurrently and sequentially | Wolchok, 2013, NEJM22 | Advanced melanoma | Phase 1 (86) | ORR 40% (21/52) (concurrent) versus 20% (6/30) (sequential) |
Pembrolizumab |
Garon, 2015, NEJM42
KEYNOTE‐001 |
NSCLC | Phase I (495) |
3.7 (all pts); 3.0 (previously untreated pts); 6.0 (previously untreated); PD‐L1 positive expression: PFS 6.3 |
Pembrolizumab | Le, 2015, NEJM27 | Mismatch repair‐deficient cancers | Phase 2 (41) | Immune‐related PFS 78% (7/9) (mismatch repair deficient) versus 11% (2/18) (mismatch proficient) colorectal cancer |
Pembrolizumab |
Ribas, 2015, Lancet Oncology
17
KEYNOTE‐002 |
Ipilimumab‐refractory melanoma | Phase 2 (540) | PFS at 6 months: 34% (2 mg/kg) versus 38% (10 mg/kg) versus 16% (ICC) |
Lambrolizumab | Hamid, 2013, NEJM15 | Advanced melanoma | Phase 1 (135) | >7.0 (all patients) |
Pembrolizumab | Robert, 2014, Lancet 16 | Ipilimumab‐refractory melanoma | Phase 1 (173) |
5.5 (pembrolizumab 2 mg/kg) versus 3.5 (10 mg/kg) Immune‐related response criteria: PFS 7.8 (2 mg/kg)versus 8.8 (10 mg/kg) |
Ipilimumab | Hodi, 2010, NEJM14 | Advanced melaonma | Phase 3 (676) | Median OS 10.0 (ipilimumab + gp100) versus 6.4 (gp100 alone) |
Ipilimumab | Robert, 2011, NEJM25 | Untreated melanoma | Phase 3 (502) | OS 11.2 (dacarbazine + ipilimumab) versus 9.1 (dacarbazine + placebo) |
Nivolumab |
Weber, 2015, Lancet Oncology
18
Checkmate 037 |
Ipilimumab or BRAF inhibitor (BRAF mutated)‐refractory melanoma | Phase 3 (272) | 4.7 (nivolumab) versus 4.2 (ICC) |
Nivolumab | Motzer, 2015, JCO28 | Clear‐cell, previously treated renal cell carcinoma | Phase 2 (168) | 2.7 (0.3 mg/kg) versus 4.0 (2 mg/kg) versus 4.2 (10 mg/kg) |
Nivolumab | Robert, 2015, NEJM19 | Untreated melanoma without BRAF mutation | Phase 3 (418) | 5.1 (nivolumab) versus 2.2 (dacarbazine) |
Nivolumab |
Rizvi, 2015, Lancet Oncology
57
Checkmate‐063 |
Advanced refractory NSCLC | Phase 2 (117) | PFS 1.9; OS 8.2 |
Nivolumab | Brahmer, 2015, NEJM58 | Advanced squamous cell NSCLC | Phase 3 (272) chemo |
3.5 (nivolumab) versus 2.8 (docetaxel) OS 9.2 (nivolumab) versus 6.0 (docetaxel) |
Nivolumab | Topalian, 2012, NEJM40 | Multiple solid tumors | Phase 1 (296) | Objective responses noted across varying doses in NSCLC, melanoma, and renal cell cancer; none in colorectal or prostate cancer |
Nivolumab | Ansell, 2015, NEJM26 | Relapsed or refractory Hodgkin's Lymphoma | Phase I (23) | PFS at 6 months, 86% |
MPDL3280A (anti‐PDL1) | Powles, 2014, Nature 39 | Metastatic bladder cancer | Phase 1 (68) | ORR at 6 weeks, 43% among PD‐L1 positive tumors and 11% for negative tumors |
MPDL3289A (anti‐PDL1) | Herbst, 2014, Nature 43 | Multiple advanced cancers | Phase 1 (277) | Objective responses (complete or partial) in all tumor types tested |
BMS‐936559 (anti‐PDL1) | Brahmer, 2012, NEJM59 | Advanced cancers | Phase 1 (207) | Objective responses seen in melanoma, NSCLC, renal cell cancer, ovarian cancer (none in colorectal or pancreatic) |
A representative, though not comprehensive, list of high‐profile clinical trials with immune checkpoint blockade is detailed. The therapy, authors and journal information, phase, and major findings are provided. BRAF‐WT: B‐raf wild‐type; ICC: investigator's choice chemotherapy; JCO, Journal of Clinical Oncology; NEJM, New England Journal of Medicine; NSCLC, non‐small‐cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression‐free survival.