Table 1.
Key features of referenced clinical trials with immune checkpoint inhibitors for advanced melanoma.
| Name clinical trial Phase |
Number of patients | Treatment plan | Primary endpoint | Median OS (95% CI) |
Median progression-free survival PFS (95% CI) |
Overall survival rates OS |
|---|---|---|---|---|---|---|
| CA184-002 Phase III [4] |
676 | G1:IPI 3 mg/kg + gp100 G2: IPI G3: gp100 Dose: Every 3 weeks for four cycles Mode: IV |
OS | IPI + gp100: 10.0 mos. (8.5-11.5) IPI: 10.1 mos. (8.0-13.8) gp100: 6.4 mos. (5.5-8.7) |
IPI + gp100: 2.76 mos. (2.73-2.79) IPI: 2.86 mos. (2.76-3.02) gp100, 2.76 mos. (2.73-2.83) |
IPI + gp100, IPI, gp100: 1 yr.: 43.6% vs 45.6% vs 25.3% 2 yrs.: 21.6%, 23.5%, 13.7% |
|
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| CA184-024 Phase III [5, 6] |
502 | G1: IPI 10 mg/kg + dacarbazine 850mg/m2 G2: dacarbazine + placebo Dose: weeks 1, 4, 7, and 10, followed by dacarbazine monotherapy every 3 weeks until week 22. Mode: IV |
OS | IPI + dacarbazine: 11.2 mos. (9.4-13.6) Dacarbazine + placebo: 9.1 mos. (7.8-10.5) |
Median values for PFS were similar in the two groups at week 12 | IPI + dacarbazine, dacarbazine: 1 yr.: 47.3% vs. 36.3% 2 yrs.: 28.5% vs. 17.9% 3 yrs.: 20.8% vs. 12.2% 5 yrs.: 18.2% vs. 8.8% |
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| Expanded access program EURO-VOYAGE [7] | 1034 | IPI 3 mg/kg | OS | 6.8 mos. (6.1-7.4) | Median PFS 2.6 mos. (2.6-2.7) | 3 yrs.: 10.9 % 4 yrs.: 8% |
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| CA184-367 III [8] |
727 | G1: IPI 3 mg/kg G2: IPI 10 mg/kg |
OS | IPI 3 mg/kg: 11.5 mos. (9.9-13.3) IPI 10 mg/kg: 15.7 mos. (6-17.8) |
IPI 3mg/kg: 2.8 mos. (2.8-2.8); IPI 10 mg/kg, 2.8 mos. (2.8-3.0) |
IPI 3 mg/kg, IPI 10 mg/kg: 1 yr.: 47.6% vs. 54.3% 2 yrs.: 31.0% vs. 38.5% 3 yrs.: 23.2% vs. 31.2% |
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| Pooled analysis from Phase II and Phase III [9] | 1861 | The majority of patients had received IPI 3 mg/kg or 10 mg/kg | OS | 11.4 mos. (10.7-12.1) | 3 yrs.: 22% for all patients, 26% for treatment-naïve patients and 20% for previously treated patients | |
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| KEYNOTE-001 Phase Ib [10–49] |
655 | PEMBRO 2 mg/kg every 3 weeks, PEMBRO 10 mg/kg every 3 weeks or PEMBRO 10 mg/kg every 2 weeks until disease progression or intolerable toxicity | CR | 23.8 mos. (20.2-30.4) | 8.3 mos. (5.8-11.1) in all treated patients 16.9 mos. (9.3-35.5) in treatment naïve patients |
3 yrs.: 42% in all treated patients; 51% in treatment-naïve patients 4 yrs.: 37% in all treated patients; 48% in treatment-naïve patients 5 yrs.: 34 % in all patients, 41% in treatment naive |
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| KEYNOTE-006 Phase III [13] |
834 | PEMBRO 10mg/kg every 2 weeks PEMBRO 10 mg/kg every 3 weeks IPI 3 mg/kg every 3 weeks for four cycles |
PFS and OS | Median OS was not reached in the resp. PEMBRO arms IPI: 16.0 mos. |
PEMBRO every 2 weeks, 5.5 mos. (3.4-6.9); PEMBRO every 3 weeks 4.1 mos. (2.9-6.9); IPI 2.8 mos. (2.8-2.9) | PEMBRO every 2 weeks, PEMBRO every 3 weeks, IPI: 1 yr.: 74.1% vs 68.4% vs 58.2% 2 yrs.: 55% vs. 55% vs. 43% |
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| Checkmate-067 Phase III [14] |
945 | NIVO 3 mg/kg or NIVO 1mg/kg + IPI 3 mg/kg every 3 weeks for 4 doses followed by NIVO 3 mg/kg every 2 weeks or IPI 3 mg/kg every 3 weeks for 4 doses | PFS | NIVO, 37.6 mos. (29.1 to not reached); NIVO + IPI not reached; IPI 19.9 mos. (16.9-24.6) | NIVO, 6.9 mos. (5.1-9.7); NIVO+IPI, 11.5 mos. (8.7-19.3); IPI, 2.9 mos. (2.8-3.2) | NIVO, NIVO+IPI, IPI: 3 yrs.: 52% vs. 58% vs. 34% 4 yrs.: 46% vs 53% vs 30% |
CI, confidence interval; CR, complete response; gp100, glycoprotein 100 peptide vaccine; IPI, ipilimumab; NIVO, nivolumab; OS, overall survival; PEMBRO, pembrolizumab; PFS, progression-free survival; mos., month; yr., year.