Table 3.
Clinical studies in melanoma.
| Patient group | Treatment | Participants (n) | Trial, ID | Outcomes | Reference |
|---|---|---|---|---|---|
| Advanced melanoma | Nivolumab + ipilimumab | 53 | Phase 1, NCT01024231 |
ORR: 40% ≥80% tumor reduction at 12 weeks: 31% Grade 3–4 AE: 53% |
Wolchok et al., 2013 (45) |
| Advanced melanoma | Nivolumab + ipilimumab | 95 (BRAF wild-type=72, BRAF V600 mutant=23) |
Phase 2, NCT01927419 (CheckMate 069) |
ORR: 61.1% | 52.2% ORR in PD-L1-positive: 58% ORR in PD-L1 negative: 55% pCR: 22.2% | 21.7% Median PFS: Not reached | 8.5 months Any grade AEs: 91% Grade 3–4 AEs: 54% |
Postow et al., 2015 (46) |
| Previously untreated metastatic melanoma | Nivolumab + ipilimumab | 314 | Phase 3, NCT01844505 (CheckMate 067) |
ORR: 57.6% Median PFS:11.5 months Median PFS in wild-type BRAF: 11.2 months Median PFS in BRAF mutation: 11.7 months Median PFS in PD-L1 positive: 14.0 months Median PFS in PD-L1 negative: 11.2 months 12 months PFS rate: 53% Grade 3–4 AEs: 55.0% |
Larkin et al., 2015 (47) |
| Melanoma brain metastases | Nivolumab + ipilimumab | 119 (asymptomatic=101, symptomatic=18) | Phase 2, NCT02320058 (CheckMate 204) |
ORR: 53.5% | 16.7% Intracranial clinical benefit: 57.4% | 16.7% Median intracranial PFS by investigator assessment: Not reached | 1.2 months 36-month intracranial PFS: 54.1% | 18.9% 36-month OS: 71.9% | 36.6% Grade 3–4 AE: 55% | 67% |
Tawbi et al., 2021 (48) |
| Asymptomatic melanoma brain metastases | Nivolumab + ipilimumab | 27 | Phase 3, NCT02460068 (NIBIT-M2) |
Median OS: 29.2 months
4-year OS: 41.0% |
Di Giacomo et al., 2021 (49) |
| Resected stage IV melanoma | Nivolumab + ipilimumab | 56 | Phase 2, NCT02523313 |
Median RFS: Not reached 1-year RFS: 75% 2-year RFS: 70% Grade 3–4 AE: 71% |
Zimmer et al., 2020 (50) |
| Resected stage IIIB-D/stage IV melanoma | Nivolumab + ipilimumab | 920 | Phase 3, NCT03068455 (CheckMate 915) |
Median RFS: Not reached 2-year RFS: 64.6% Median OS: Not reached 2-year OS: 89.9% Median DMFS: Not reached 2-year DMFS: 75.4% Grade 3–4 AE: 32.6% |
Weber et al., 2022 (51) |
| Resectable stage III melanoma | Nivolumab + ipilimumab | 212 | Phase 3, NCT04949113 |
Estimated 12-month event free survival: 83.7% MPR: 59% Grade 3–4 AE: 29.7% |
Blank et al., 2024 (52) |
| Metastatic uveal melanoma | Nivolumab + ipilimumab | 33 | Phase 2, NCT01585194 (PROSPER) |
ORR: 18% Median PFS: 5.5 months Median OS: 19.1 months 1-year OS: 56% Grade 3–4 AE: 40% |
Pelster et al., 2020 (53) |
| Metastatic uveal melanoma | Nivolumab + ipilimumab | 52 | Phase 2, NCT02626962 (GEM-1402) |
ORR: 11.5% Median PFS: 3.0 months 6-month PFS: 28.8% 12-month PFS: 19.2% Median OS: 12.7 months 12-month OS: 51.9% 24-month OS: 26.4% Grade ≥ 3 AE: 57.7% |
Piulats et al., 2021 (54) |
| Advanced melanoma | Pembrolizumab + ipilimumab | 153 | Phase 1b, NCT02089685 (KEYNOTE-029) |
ORR: 61% Median PFS: Not reached 1-year PFS: 69% Median OS: Not reached 1-year OS: 89% Grade 3–4 AE: 45% |
Long et al., 2017 (55) |
AE, adverse event; DMFS, distant metastasis-free survival; MPR = major pathological response; ORR, objective response rate; OS, overall survival; pCR, pathological complete response; PFS, progression-free survival; RFS, recurrence-free survival.