Study | Phase | Patient population* | Duration of survival follow-up, months | Arm† (n), dosing schedule | Median PFS, months (95% CI) | Longest landmark PFS rate | Median OS, months (95% CI) | Longest landmark OS rate |
Immune checkpoint inhibitors | ||||||||
CheckMate 06712 | III | Any BRAF | 60 (minimum) | NIVO+IPI (314), NIVO 1 mg/kg+IPI 3 mg/kg Q3W×4, then NIVO 3 mg/kg Q2W | 11.5 (8.7 to 19.3) | 5 years: 36% | NR (38.2 to NR) | 5 years: 52% |
NIVO (316), NIVO 3 mg/kg Q2W | 6.9 (5.1 to 10.2) | 5 years: 29% | 36.9 (28.2 to 58.7) | 5 years: 44% | ||||
IPI (315), IPI 3 mg/kg Q3W×4 | 2.9 (2.8 to 3.2) | 5 years: 8% | 19.9 (16.8 to 24.6) | 5 years: 26% | ||||
CheckMate 06616 | III | BRAF wild-type | 60 (minimum) | NIVO (210), NIVO 3 mg/kg Q2W | 5.1 (3.5 to 12.2) | 5 years: 28% | 37.3 (25.4 to 51.6) | 5 years: 39% |
KEYNOTE-0065 | III | Any BRAF
Data shown are for the treatment-naive patient subgroup | 57.7 (median) | PEMBRO (368), PEMBRO 10 mg/kg Q2W/Q3W | 11.6 (8.2 to 16.4) | 4 years: 26% (Q2W), 28% (Q3W) | 38.7 (27.3 to 50.7) | 5 years: 41% (Q2W), 45% (Q3W) |
IPI (181), IPI 3 mg/kg Q3W×4 | 3.7 (2.8 to 4.3) | NA | 17.1 (13.8 to 26.2) | NA | ||||
CA184-16944 | III | Any BRAF | 43 (minimum) | IPI 10 mg/kg (365), IPI 3 mg/kg (362), Q3W×4 | 2.8 (2.8 to 3.0), 2.8 (2.8 to 2.8) | NA | 15.7 (11.6 to 17.8), 11.5 (9.9 to 13.3) | 3 years: 31%, 23% |
KEYNOTE-00111 | I | Any BRAF
Data shown are for the treatment-naive patient subgroup | 55 (median) | PEMBRO (151), PEMBRO 2 mg/kg Q3W/10 mg Q2W/10 mg Q3W | 16.9 (9.3 to 35.5) | 5 years: 29% | 38.6 (27.2 to NR) | 5 years: 41% |
CA209-00445 | I | Any BRAF
No prior immune checkpoint inhibitor | 43.1 (median) | NIVO+IPI (94), Dose-escalation study‡ | NA | NA | NR (40.9 to NR) | 4 years: 57% |
CA209-00317 | I | Previously treated, advanced melanoma (any BRAF), RCC, or NSCLC (only melanoma data shown) | 58.3 (minimum) | NIVO (107), Dose escalation 0.1 to 10 mg/kg Q2W | NA | NA | 20.3 (12.5 to 37.9) | 5 years: 34% |
IPI-pooled analysis46 | II/III | Various | Approx. 11 (median) | IPI (1861), Most patients received 3 or 10 mg/kg | NA | NA | 11.4 (10.7 to 12.1) | 3 years: 22% |
Other immunotherapy | ||||||||
IL-2 pooled analysis19 | Various | Various | 62 (median) | High-dose IL-2 (270), 600,000 or 720,000 IU/kg | NA | NA | 11.4 (NA) | NA |
ACT+IL-225 | Various | Previously treated, advanced melanoma | 62 (median) | Autologous tumor-infiltrating lymphocytes+IL-2 after a lymphodepletion | NA | NA | NA | 5 years: 29% |
Combination-targeted therapy | ||||||||
COMBI-d and COMBI-v15 | III | BRAF-mutant | 22 (median) | DAB +TRAM (563), DAB 150 mg twice daily+TRAM 2 mg once daily | 11.1 (9.5 to 12.8) | 5 years: 19% | 25.9 (22.6 to 31.5) | 5 years: 34% |
COLUMBUS13 | III | BRAF-mutant | 48.8 (median) | ENCO+BINI (192), ENCO 450 mg once daily+BINI 45 mg twice daily | 14.9 (11.0 to 20.2) | 3 years: 29% | 33.6 (24.4 to 39.2) | 3 years: 47% |
VEM (191), VEM 960 mg twice daily | 7.3 (5.6 to 7.9) | 3 years: 14% | 16.9 (14.0 to 24.5) | 3 years: 31% | ||||
ENCO (194),
ENCO 300 mg once daily | 9.6 (7.4 to 14.8) | 3 years: 25% | 23.5 (19.6 to 33.6) | 3 years: 41% | ||||
coBRIM14 | III | BRAF-mutant | NA | COBI+VEM (247), COBI 60 mg once daily+VEM 960 mg twice daily | 12.6 (9.5 to 14.8) | 5 years: 14% | 22.5 (20.3 to 28.8) | 5 years: 31% |
VEM (248), VEM 960 mg twice daily | 7.2 (5.6 to 7.5) | 5 years: 10% | 17.4 (14.5 to 19.8) | 5 years: 26% |
*Trials were conducted solely in treatment-naive patients unless indicated.
†Data for control arms are only included if ipilimumab or a targeted therapy was the comparator.
‡NIVO+IPI Q3W×4 (mg/kg) in one of the following cohorts: (1) NIVO 0.3+IPI 3; (2) NIVO 1+IPI 3; (2a) NIVO 3+IPI 1; (3) NIVO 3+IPI 3; (8) NIVO 1+IPI 3. Cohorts 1 to 3 received maintenance with NIVO Q3W×4, then NIVO+IPI Q12W×8.
ACT, adoptive cell transfer; BINI, binimetinib; COBI, cobimetinib; DAB, dabrafenib; ENCO, encorafenib; IL-2, interleukin-2; I-O, immuno-oncology; IPI, ipilimumab; NA, not available; NIVO, nivolumab; NR, not reached; NSCLC, non-small cell lung cancer; OS, overall survival; PEMBRO, pembrolizumab; PFS, progression-free survival; Q2W, every 2 weeks; Q3W, every 3 weeks; RCC, renal cell carcinoma; TRAM, trametinib; VEM, vemurafenib.