Table 1.
Selected clinical trials of CTLA-4 and PD-1 pathway blocking antibodies in advanced melanoma.
| Agent tested | Patients | Treatment arms | Response ratesa | Survival |
|---|---|---|---|---|
| CTLA-4 BLOCKADE | ||||
| Ipilimumab (8) | 676 patients with previously treated advanced melanoma | Ipilimumab vs. gp100 peptide vaccine vs. combination | Ipilimumab alone: ORR 10.9% | Ipilimumab alone: median OS: 10.1 months |
| 45.6% at 1 year | ||||
| 23.5% at 2 years | ||||
| Ipilimumab dosed at 3 mg/kg every 3 weeks × 4 doses | Gp100 vaccine: ORR 1.5% | Gp100 vaccine: Median OS: 6.4 months | ||
| 25.3% at 1 year | ||||
| 13.7% at 2 years | ||||
| PD-1 BLOCKADE | ||||
| Pembrolizumab (21) | 173 patients with advanced melanoma whose disease had progressed after ipilimumab | Pembrolizumab 2 mg/kg every 3 weeks vs. pembrolizumab 10 mg/kg every 3 weeks | For total study population: ORR 26% | 2 mg/kg dose: 58% at 1 year |
| 10 mg/kg dose: 63% at 1 year | ||||
| Nivolumab (20) | 418 Treatment naive patients with BRAF wild-type advanced melanoma | Nivolumab 3 mg/kg every 2 weeks vs. dacarbazine | Nivolumab: ORR: 40% | Nivolumab: median OS: NR |
| 72.9% at 1 year | ||||
| Dacarbazine: ORR: 13.9% | Dacarbazine: median OS: 10.8 months | |||
| 42.1% at 1 year | ||||
| COMBINATION | ||||
| Ipilimumab + nivolumab (30, 31) | 52 patients with advanced melanoma (cohorts 1, 2, 2A, 3) | Multiple dose cohorts: ipilimumab 1–3 mg/kg + nivolumab 0.3–3 mg/kg | Across all dose levels: ORR: 40% (21–53%) | Across all dose levels: median OS: NR |
| 85% at 1 year | ||||
| 79% at 2 years | ||||
NR, not reached; OS, overall survival; ORR, objective response rate.
a The Hodi et al. and Wolchok et al. studies used mWHO to measure response, other studies listed used RECIST criteria.