Table 3.
Phase II/III studies of CTLA-4 blockade in melanoma.
| Study reference | Number of patients eligible for analysis | Study design | Primary end point | Dose and schedule - treatment arm | Responses | OS/PFS | HR (95% CI) |
|---|---|---|---|---|---|---|---|
| BMS 008 [79] | 155 | Phase II, open-label, single arm, advanced melanoma | Dose-finding | IPI 10 mg/kg | 47% (1 year) | N/A | N/A |
| BMS 022 [80] | 217 | Phase II, randomized, double-blind, advanced melanoma | Efficacy of three dose levels of IPI | IPI at varying doses (0.3, 3, 10 mg/kg) Induction 0.3/3/10 mg/kg q3weeks for 4 doses Maintenance 0.3/3/10 mg/kg q6weeks until week 48 then q12weeks afterward |
48% (1 year) | N/A | N/A |
| BMS 007 [81] | 115 | Phase II, randomized, double-blind, advanced melanoma | Rate of grade II + diarrhea | IPI 10 mg/kg | 51% (1 year) | N/A | N/A |
| Medarex MDX010–20 [2] | 676 | Phase III, randomized, double-blind, advanced melanoma | ORR, subsequently amended to OS | IPI 3 mg/kg + GP-100 peptide vaccine vs IPI alone vs GP-100 peptide vaccine alone | IPI alone: 10.9% IPI + GP-100: 5.7% GP-100 alone: 1.5% |
OS rates (1/2 year): IPI alone: 45.6/23.5% IPI + GP-100: 43.5/21.6% GP-100 alone: 25.3/13.7% OS duration: IPI alone: 10.1 months IPI + GP-100: 10.0 months GP-100 alone: 6.4 months PFS duration: IPI alone: 2.86 months IPI + GP-100: 2.76 months GP-100 alone: 2.76 months |
IPI alone (compared with GP-100 alone): 0.66 (95% CI 0.51 – 0.87) IPI + GP-100 (compared with GP-100 alone): 0.68 (95% CI 0.55 – 0.85) |
| BMS 024 [3] | 502 | Phase III, randomized, double-blind, advanced melanoma | OS | IPI + DTIC: induction 10 mg/kg + DTIC (850 mg/m2) q3weeks for four doses Maintenance 10 mg/kg + DTIC (850 mg/m2) q12weeks |
IPI + DTIC: 33.2% (DCR), 15.2% (ORR) DTIC alone: 30.2% (DCR), 10.3% (ORR) |
OS rates (1/2/3 year): IPI + DTIC: 47.3/28.5/20.8% DTIC alone: 36.3/17.9/12.2% OS duration: IPI + DTIC: 11.2 months DTIC alone: 9.1 months PFS duration: IPI + DTIC: 2.8 months DTIC alone: 2.6 months |
IPI + DTIC: OS 0.72, PFS 0.76 |
| Sarnaik et al. [82] | 75 | Phase II, single-arm, open-label, resected high-risk melanoma | 40% rate of tolerable IRAEs | HLA A*0201 positive: IPI 3 or 10 mg/kg q8weekly for 12 months + multipeptide (MART-1/GP-100/tyrosinase) vaccine HLA A*0201 negative: IPI 10 mg/kg q8weekly for 12 months |
Not reached (29.5 months follow-up) | Resected stage IV: 40.5 months Resected stage IIIc: not reached (29.5 months follow-up) |
Not reached (29.5 months follow-up) |
| Margolin et al. [83], | 72 | Phase II, single-arm, open-label, advanced melanoma with brain metastases 2 cohorts: cohort A (asymptomatic; no steroids) and cohort B (symptomatic, on stable dose of steroids) |
DCR | IPI: induction 10 mg/kg q3weeks for 4 doses Maintenance 10 mg/kg q12weeks |
Cohort A: 18% Cohort B: 10% |
N/A | N/A |
| NIBIT-M1 [84] | 84 | Phase II, single-arm, open-label, advanced melanoma | Immune-response DCR using IRRC | IPI + fotemustine: IPI induction 10 mg/kg q3weeks for 4 doses Maintenance 10 mg/kg + DTIC (850 mg/m2) q12weeks Fotemustine 100 mg/m2 qweekly for 3 weeks then q3weekly | IRORR - 29.1% OS at 1 year 51.8% (median OS not reached) |
Median IRPFS 5.3 months | Not reported |
CI: Confidence interval; DCR: Disease control rate; HR: Hazard ratio; IPI: Ipilimumab; IRAEs: Immune-related adverse events; IRRC: Immune-related response criteria; N/A: Not applicable ORR: Overall response rate; OS: Overall survival; PFS: Progression-free survival.