Table 2.
Notable clinical trials with published results for papillary renal cell carcinoma
| Trial | Enrollment criteria | Number of pRCC | Intervention | Results |
|---|---|---|---|---|
|
| ||||
| Single-agent TKI | ||||
| NCT02761057 (PAPMET)92 | Up to one prior systemic therapy excluding VEGF and MET inhibitor | 147 (90 for cabozantinib vs. sunitinib) | Cabozantinib vs. sunitinib (savolitinib and crizotinib arms closed) | ORR: 23% vs. 4% (p=0.010) Median PFS: 9.0 vs. 5.6 m (HR 0.60, 95% CI 0.37–0.97, p=0.019) Median OS: 20.0 vs. 16.4 m (HR 0.84, 95% CI 0.47–1.51) |
| NCT03091192 (SAVOIR)103 | MET driven, no prior therapy | Savolitinib 33 Sunitinib 27 |
Savolitinib vs. sunitinib | ORR: 27% (95% CI 13.3–45.5) vs. 7% (95% CI 0.9–24.3) PFS: 7.0 (95% CI 2.8 to not calculated [NC] m vs. 5.6 m [95% CI 4.1–6.9]) |
|
| ||||
| Single-agent ICI | ||||
| NCT02853344 (Keynote-427)96 | No prior systemic therapy | 118 (71.5%) | Pembrolizumab | ORR: 28.8% Median PFS: 5.5 m (95% CI 3.9–6.9) Median OS: 31.5 m (95% CI 25.5–NR) |
| NCT03117309 (HCRN GU16-260-Cohort B)93 | No prior systemic therapy | 19 (54%) | Nivolumab (part A), then with ipilimumab if refractory to monotherapy (part B) | ORR: 1/19 (5%) in part A |
| NCT02596035 (CheckMate 374)94 | Prior systemic therapy allowed | 24 (54.5%) | Nivolumab | ORR: 8.3% |
| NCT03012581 (AcSe) 95 | Prior systemic therapy allowed | pRCC type 2: 20 (41%), pRCC type I and unclassified 9 (18%) | Nivolumab | ORR: 10% (pRCC type 2: 5% pRCC type 1 and unclassified: 11%) |
|
| ||||
| Combination ICI | ||||
| NCT02982954 CheckMate 920102 | No prior systemic therapy | 18 (34.6%) | Nivolumab with ipilimumab | ORR:27.8%* *Assuming all 18 were included in ORR (only 46/52 patients were included) |
| NCT03075423 SUNNIFORECAST104 | No prior systemic therapy | 178 (57.6%) | Nivolumab with ipilimumab | ORR: 29.2% |
|
| ||||
| Combination ICI and TKI | ||||
| NCT03635892 (CA209-9KU)97 | No prior ICIs | 32 | Cabozantinib with nivolumab | ORR: 48% (95% CI 30–64) Median PFS: 13 m (95% CI 7.9–16.9) |
| NCT04704219 (Keynote-B61)98 | No prior therapy | 93 (59%) | Pembrolizumab plus lenvatinib | ORR: 54% (95% CI 43–64) Median PFS: 17.5 m (15–NR) |
| NCT03170960 (COSMIC-021)99 | No prior ICIs or MET inhibitors | 15 (47%) | Cabozantinib with atezolizumab | ORR: 47% Median PFS: 8.1 m (95% CI 2.7–18.4) Median OS: 31.8 (95% CI 6.1–NR) |
| NCT02819596 (CALYPSO)100 | No prior ICIs or MET inhibitors | 41 | Savolitinib with durvalumab | ORR: 29% (95% CI 16–46) Median PFS: 4.9 m (95% CI 2.5–10) Median OS: 14.1 m (95% CI 7.3–30.7) |
|
| ||||
| Combination TKI and mTOR inhibitor | ||||
| NCT01108445 (ASPEN)101 | No prior systemic treatment | Everolimus: 37 (65%) Sun: 33 (65%) |
Everolimus plus lenvatinib vs. sunitinib | ORR: Everolimus: 2 (5%) Sun: 8 (24%) |
| NCT02915783105 | No prior systemic treatment | 20 (65%) | Lenvatinib Plus Everolimus | ORR: 15% Median PFS: 9.2 m (95% CI 3.5–NE) Median OS: 11.7 m (95% CI 8.1–NE) |
|
| ||||
| Combination ICI and anti-angiogenic | ||||
| NCT02724878106 | Prior systemic therapy allowed but not ICI or bevacizumab | 12 (35%) | Atezolizumab with bevacizumab | ORR: 25% (0.039–0.539) |
CI: confidence interval; HR: hazard ratio; ICI: immune checkpoint inhibitors; NE: not evaluable; NR: not reported; ORR: objective response rate; OS: overall survival; PFS: progression-free survival; RCC: renal cell carcinoma; TKI: tyrosine kinase inhibitor; VGEF: vascular endothelial growth factor.