Table 1. Single agent anti-PD-1, anti-PD-L1 and anti-CTLA-4 studies in aRCC.
| Trial | Trial summary | Number of patients (RCC) | Dose of trial drug | ORR (%) | Median progression- free survival (PFS) (months) | Median OS (months) | Immune-related G3/4 toxicities |
|---|---|---|---|---|---|---|---|
| Nivolumab (fully human IgG4 anti-PD-1 mAb) | |||||||
| NCT00730639 McDermott et al. [87] | Phase I study in patients with advanced solid tumours with a RCC cohort | 296 (34) | 1 mg/kg | 24% | NR | All patients: 22.4; 4-year survival rate: 38% | 18% |
| 10 mg/kg | 31% | ||||||
| Every 2 weeks | |||||||
| NCT01354431 Motzer et al. [82] | Phase II study in aRCC. Patients randomly assigned in one of three dose groups | 168 (168) | 0.3 mg/kg | 20% | 2.7 | 18.2 | 11% (n=19) |
| 2 mg/kg | 22% | 4.0 | 25.5 | ||||
| 10 mg/kg | 20% | 4.2 | 24.7 | ||||
| Every 3 weeks | Four-year survival rate: 29% | ||||||
| Checkmate 025 NCT01668784 Motzer et al. [83] | Randomized, open-label phase III study of nivolumab compared with everolimus in patients with aRCC who had received ≥1 prior regime of anti-angiogenic therapy | Nivolumab (406) | 3 mg/kg | 25% | 4.6 m | 25 | 19% (76/406) |
| Every 2 weeks | Improved health related QoL | All G3/4 AEs 20% | |||||
| Everolimus (415) | 10 mg OD | 5% | 4.4 | 19.6 (P=0.002) | NR | ||
| All G3/4 AEs: 37% | |||||||
| Atezolizumab (human IgG1 anti-PD-L1 mAb) | |||||||
| NCT01374842 McDermott et al. [88] | Phase Ia dose-escalation and dose-expansion study with a RCC cohort. | (70) | 10, 15, 20mg/kg every 3 weeks | All G3/4 AEs: 17% | |||
| ccRCC 63 | 15% | 5.6 | 28.9 | 4% | |||
| nccRCC 7 | 0% | NR | NR | NR | |||
| BMS-936559, MDX-1105 (fully human IgG4 anti-PD-L1 mAb) | |||||||
| NCT0072966 Brahmer et al. [89] | Phase I dose-escalation and dose-expansion study in patients with advanced solid tumours including an RCC cohort | 207 (17) | 10 mg/kg | 12% | Stabilization of disease at 24 weeks in 41% | NR | All G3/4 AEs: 5% |
| Ipilimumab (fully human IgG1 anti-CTLA-4 mAb) | |||||||
| Yang et al. [86] | Single institution, phase II study of patients with mRCC. Patients were allowed to have had prior treatment with IL-2 | Cohort A (21) | 3 mg/kg loading | 5% | NR | NR | Both groups: 33% |
| Then 1 mg/kg | Colitis: 28% | ||||||
| Every 3 weeks | Hypophysitis: 5% | ||||||
| Cohort B (40) | 3 mg/kg all doses | 12.5% | NR | NR | |||
| Every 3 weeks | |||||||
| Tremelimumab (fully human IgG2 anti-CTLA-4 mAb) | |||||||
| Ribas et al. [90] | Phase I dose escalation study of patients with advanced melanoma, RCC or colorectal cancer (CRC) | 39 (4) | MTD: 15 mg/kg | NR | NR | NR | |
Abbreviations: MTD, maximum tolerated dose; NR, not reached.