Table 1.
Characteristics of included studies.
| Trial | Phase | Treatment arm | Control arm | Treatment (N) | Previous treatment (N) |
|---|---|---|---|---|---|
| Pembrolizumab and Ipilimumab | |||||
| KEYNOTE-029 | 1 | Pembrolizumab 2 mg/kgQ3wks (up to 2 years) + ipilimumab 1 mg/kgQ3wks for 4 doses | NA | 153 | 20 prior systemic therapy |
| Pembrolizumab | |||||
| KEYNOTE-001 | 1 | Pembrolizumab 2 mg/kgQ3wks | NA | 89 | 342 prior ipilimumab therapy 342 prior systemic therapy |
| Pembrolizumab 10 mg/kgQ3wks | 172 | ||||
| Pembrolizumab 10 mg/kgQ2wks | 81 | ||||
| Pembrolizumab 2 mg/kgQ3wks | 73 | 0 prior ipilimumab therapy 152 prior systemic therapy | |||
| Pembrolizumab 10 mg/kgQ3wks | 141 | ||||
| Pembrolizumab 10 mg/kgQ2wks | 99 | ||||
| KEYNOTE-041 | 1 | Pembrolizumab 2 mg/kgQ3wks | NA | 42 | 0 prior ipilimumab therapy 30 prior systemic therapy |
| NCT02085070 | 2 | Pembrolizumab 10 mg/kgQ2wks | NA | 23 | 13 prior ipilimumab therapy 16 prior systemic therapy |
| KEYNOTE-002 | 2 | Pembrolizumab 2 mg/kgQ3wks | chemotherapy | 178 | 178 prior ipilimumab therapy 178 prior systemic therapy |
| Pembrolizumab 10 mg/kgQ3wks | 179 | 179 prior ipilimumab therapy 178 prior systemic therapy | |||
| KEYNOTE-006 | 3 | Pembrolizumab 10 mg/kgQ2wks | ipilimumab 3 mg/kgQ3wks for 4 doses | 278 | 0 prior ipilimumab therapy 96 prior systemic therapy |
| Pembrolizumab 10 mg/kgQ3wks | 277 | 0 prior ipilimumab therapy 91 prior systemic therapy | |||
| Nivolumab and Ipilimumab (concomitant) | |||||
| CA209–004 | 1 | Nivolumab 0.3 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 0.3 mg/kgQ3wks for 4 doses then nivolumab 0.3 mg/kg+ ipilimumab 3 mg/kgQ12wks for 8 doses | NA | 14 | 0 prior ipilimumab therapy 42 prior systemic therapy |
| Nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 1 mg/kgQ3wks for 4 doses then nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ12wks for 8 doses | 17 | ||||
| Nivolumab 3 mg/kg+ ipilimumab 1 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kg+ ipilimumab 1 mg/kgQ12wks for 8 doses | 16 | ||||
| Nivolumab 3 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kg+ ipilimumab 3 mg/kgQ12wks for 8 doses | 6 | ||||
| Nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 1 mg/kgQ3wks for up to 48 doses | 41 | ||||
| CheckMate-069 | 2 | Nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kgQ2wks | Ipilimumab 3 mg/kgQ3wks for 4 doses | 94 | 0 prior systemic therapy |
| CheckMate-204 | 2 | Nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kgQ2wks | NA | 94 | 16 prior systemic therapy |
| NCT02374242 | 2 | Nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kgQ2wks | Nivolumab 3 mg/kgQ2wks | 35 | 8 prior systemic therapy |
| CheckMate-067 | 3 | Nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kgQ2wks | Nivolumab 3 mg/kgQ2wks OR ipilimumab 3 mg/kgQ3wks for 4 doses | 313 | 0 prior systemic therapy |
| Nivolumab and Ipilimumab (Sequential of ipilimumab then nivolumab) | |||||
| CA209–004 | 1 | Ipilimumab followed by nivolumab 1 mg/kg(within 4–12wks of last dose of ipilimumab | NA | 17 | 33 prior ipilimumab therapy 33 prior systemic therapy |
| Ipilimumab followed by nivolumab 3 mg/kg(within 4–12wks of last dose of ipilimumab | 16 | ||||
| CA209–064 | 2 | Induction period 1 (ipilimumab 3 mg/kgQ3wks up to 4 doses during weeks 1–13). Induction period 2 (nivolumab 3 mg /kg Q2wks up to 6 doses during weeks 13–25) Continuation period (nivolumab 3 mg/kgQ2wks from week 25 till completion of 2 years) | Nivolumab followed by ipilimumab | 70 | 0 prior systemic therapy |
| Nivolumab and Ipilimumab (Sequential of nivolumab then ipilimumab) | |||||
| CA209–064 | 2 | Induction period 1 (nivolumab 3 mg/kgQ2wks up to 6 doses during weeks 1–13). Induction period 2 (ipilimumab 3 mg /kg Q3wks up to 4 doses during weeks 13–25) Continuation period (nivolumab 3 mg/kgQ2wks from week 25 till completion of 2 years) | Ipilimumab followed by nivolumab | 68 | 0 prior systemic therapy |
| Nivolumab | |||||
| CA209–003 | 1 | Nivolumab 3 mg/kgQ2wks | NA | 107 | 69 prior immunotherapy 107 prior systemic therapy |
| CA209–006 | 1/2 | Nivolumab 3 mg/kgQ2wks for 24 weeks then Q12wks for up to 2 years | NA | 61 | 61 prior ipilimumab therapy 31 prior systemic therapy |
| JapicCTI-142533 | 2 | Nivolumab 3 mg/kgQ2wks | NA | 23 | 0 prior systemic therapy |
| NCT02374242 | 2 | Nivolumab 3 mg/kgQ2wks | Nivolumab 1 mg/kg+ Ipilimumab 3 mg/kgQ3wks for 4 doses then Nivolumab 3 mg/kgQ2wks | 41 | 18 prior systemic therapy |
| CheckMate 066 | 3 | Nivolumab 3 mg/kgQ2wks | Dacarbazine | 206 | 33 prior systemic therapy |
| CheckMate 067 | 3 | Nivolumab 3 mg/kgQ2wks | Nivolumab +ipilimumab OR ipilimumab 3 mg/kgQ3wks for 4 doses | 313 | 0 prior systemic therapy |
| CheckMate 037 | 3 | Nivolumab 3 mg/kgQ2wks | Investigator's choice of chemotherapy. | 268 | 268 prior ipilimumab therapy |
| Ipilimumab | |||||
| Downey et. al | 1 | Ipilimumab 3 mg/kg can be escalated to 5 mg/kg then to 9 mg/kg if no objective response | NA | 66 | 57 prior systemic therapy |
| Maker et.al | 1 | Ipilimumab 3 mg/kg can be escalated to 5 mg/kg then to 9 mg/kg if no objective response | NA | 46 | 29 prior chemotherapy 2 prior hormonal therapy 38 prior immunotherapy, |
| CA184–078 | 1 | Ipilimumab 10 mg/kgQ3wks for 4 doses + placebo | Ipilimumab + dacarbazine OR ipilimumab + paclitaxel+carboplatin | 20 | 0 prior systemic therapy |
| CA184–087 | 1 | Ipilimumab 10 mg/kgQ3wks for 4 doses | NA | 75 | |
| CA184–013 | 2 | Ipilimumab 3 mg/kgQ3wks for 4 doses | Ipilimumab + dacarbazine | 39 | 0 prior chemotherapy 19 prior immunotherapy |
| CA184–169 | 3 | Ipilimumab 3 mg/kgQ3wks for 4 doses | NA | 362 | 205 prior systemic therapy |
| Ipilimumab 10 mg/kgQ3wks for 4 doses | 364 | 206 prior systemic therapy | |||
| CA184–396 | 2 | Ipilimumab 3 mg/kgQ3wks for 4 doses | NA | 20 | 16 prior systemic therapy |
| CheckMate 067 | 3 | Ipilimumab 3 mg/kgQ3wks for 4 doses | Nivolumab +ipilimumab OR nivolumab 3 mg/kgQ2wks | 311 | 0 prior systemic therapy |
| CheckMate-069 | 2 | Ipilimumab 3 mg/kgQ3wks for 4 doses | Nivolumab 1 mg/kg+ ipilimumab 3 mg/kgQ3wks for 4 doses then nivolumab 3 mg/kgQ2wks | 46 | 0 prior systemic therapy |
| KEYNOTE-006 | 3 | Ipilimumab 3 mg/kgQ3wks for 4 doses | Pembrolizumab 10 mg/kgQ2wks | 256 | 0 prior ipilimumab therapy 97 prior systemic therapy |
| pembrolizumab 10 mg/kgQ3wks | |||||
| CA184–001 (MDX010–15) | 1/2 | Ipilimumab 3 mg/kg or 2.8 or 5 mg/kg on Days 1, 57, and 85 | NA | 34 | 31 prior systemic therapy |
| Single dose of ipilimumab 7.5, 10, 15, or 20 mg/kg | 30 | 21 prior systemic therapy | |||
| Ipilimumab 10 mg/kgQ3wks for 4 doses | 24 | 18 prior systemic therapy | |||
| NCT01134614 | 2 | Ipilimumab 10 mg/kgQ3wks for 4 doses then Q12wks | Ipilimumab + sargramostim | 120 | 54 prior systemic therapy |
| NCT01216696 | 2 | Ipilimumab 10 mg/kgQ3wks for 4 doses then Q12wks | NA | 25 | 19 prior systemic therapy |
| NCT01355120 | 2 | Ipilimumab 3 mg/kgQ3wks for 4 doses | NA | 103 | 103 prior systemic therapy |
| NCT01740297 | 2 | Ipilimumab 3 mg/kgQ3wks for 4 doses | Ipilimumab+ talimogene laherparepvec | 95 | 29 prior anticancer therapy |
| CA184–004 | 2 | Ipilimumab 3 mg/kgQ3wks for 4 doses then Q12 | NA | 40 | 29 prior systemic therapy |
| Ipilimumab 10 mg/kgQ3wks for 4 doses then Q12wks | 42 | 33 prior systemic therapy | |||
| CA184–007 | 2 | Ipilimumab 10 mg/kgQ3wks for 4 doses + placebo | Ipilimumab + budesonide | 57 | 41 prior systemic therapy |
| CA184–008 | 2 | Ipilimumab 10 mg/kgQ3wks for 4 doses then Q12wks | NA | 155 | 155 prior systemic therapy |
| CA184–022 | 2 | Ipilimumab 0.3 mg/kgQ3wks for 4 doses then Q12wks | NA | 72 | 72 prior systemic therapy |
| Ipilimumab 3 mg/kgQ3wks for 4 doses then Q12wks | 71 | 71 prior systemic therapy | |||
| Ipilimumab 10 mg/kgQ3wks for 4 doses then Q12wks | 71 | 71 prior systemic therapy | |||
| MDX010–20 | 3 | Ipilimumab 10 mg/kgQ3wks for 4 doses then Q12wks if patients met the re-induction criteria | Ipilimumab + gp100 or gp100 alone | 131 | 131 prior systemic therapy |
| CA184–042 | 2 | Ipilimumab 10 mg/kgQ3wks for 4 doses then Q12wks | Ipilimumab+ corticosteroids | 51 | 40 prior systemic therapy |
N, number of patients.