Trial | Description | Results (combination vs. SOC), 95% CI | ||
---|---|---|---|---|
OS | PFS (months) | Objective Response | ||
CheckMate 025(NCT01668784)[16] | Nivolumab vs. Everolimus | PD-L1 τ (< 1%) amOS: 27.4 vs. 21.2 mo (HR 0.77; 0.60 to 0.97)PD-L1 τ (≥1%) amOS: 21.8 vs. 18.8 mo (HR 0.79; 0.53 to 1.17 | ||
CheckMate 214(NCT02231749)[9] | Nivolumab + Ipilimumab vs. Sunitinib | PD-L1 τ (< 1%) aHR 0.73; 95% CI, 0.56 to 0.9612-mo rate: 80% vs. 75%18-mo rate; 74% vs. 64%PD-L1 τ (≥1%) aHR 0.45; 0.29 to 0.7112-mo rate: 86% vs. 66%18-mo rate: 81% vs. 53%Sarcomatoid HistologyHR 0.56; 0.38–0.83PD-L1 (≥1%) prevalence: 50% (SH) vs. 27.5% (non-SH) | PD-L1 τ (< 1%) amPFS: 11.0 vs. 10.4 (HR 1.00; 0.8 to 1.26)PD-L1 τ (≥1%) amPFS: 22.8 vs. 5.9 (HR 0.46; 0.31 to 0.67) | PD-L1 τ (< 1%) aORR: 37% vs. 28%, p = 0.03PD-L1 τ (≥1%) aORR: 58% vs. 22%, p < 0.001Sarcomatoid HistologyORR: 56.7% vs. 19.2%, P < .0001CR: 18.3% vs. 0% |
Keynote-426(NCT02853331)[11] [insert ASCO abstract 4500] | Pembrolizumab + Axitinib vs. Sunitinib | PD-L1 β (< 1%) bHR 0.59; 0.34 to 1.03PD-L1 β (≥1%) bHR 0.54; 0.35 to 0.84Sarcomatoid Histology12-mo OS: 83.4% vs 79.5% (HR 0.58; 0.21 to 1.59) | PD-L1 β (< 1%) bHR 0.87; 0.62 to 1.23PD-L1 β (≥1%) bHR 0.62; 0.47 to 0.80Sarcomatoid HistologymPFS: NR vs. 8.4 (HR 0.54; 0.29 to 1.00) | Sarcomatoid HistologyORR: 58.8% vs 31.5%CR: 11.8% vs. 0% |
Javelin RENAL 101(NCT02684006)[12, 13] | Avelumab + Axitinib vs. Sunitinib | Not available. | PD-L1¥ + (≥1%) cmPFS: 13.8 vs 7.2 (HR 0.61; 0.47 to 0.79; P < 0.001)PD-L1¥- (< 1%) cmPFS: 16.1 vs. 11.1 | PD-L1¥ + (≥1%) cORR: 55.2% vs 25.5%CR: 4.4% vs. 2.1%PD-L1¥- (< 1%) cORR: 47% vs. 28% |
IMmotion150[46] | Atezolizumab + Bevacizumab or Atezolizumab monotherapy vs. Sunitinib | Not available. | ITT PopulationCombination HR 1.0; 0.69 to 1.45Monotherapy HR 1.19; 0.82 to 1.71PD-L1¥ + (≥1%) dCombination HR 0.64; 0.38 to 1.08Monotherapy HR 1.03; 0.63 to 1.67 | PD-L1¥ + (≥1%) d48% (combination) and 28% (monotherapy) vs. 27% |
IMmotion151(NCT02420821)[14] [insert ASCO abstract citation] | Atezolizumab + Bevacizumab vs. Sunitinib | PD-L1¥ + (≥1%) dOS: 75% vs. 65% (HR 0.68; 0.46–1.0; p = 0.0470)Sarcomatoid HistologyAll SarcmOS: NR vs. 15.0 (HR: 0.56; 0.32 to 0.96)12-mo OS: 69% vs. 60%PD-L1+ SarcmOS: NR vs. 15.0 (HR: 0.53; 0.27 to 1.06)12-mo OS: 71% vs. 61% | PD-L1¥ + (≥1%) dmPFS: 11.2 vs. 7.7 (HR 0.74; 0.57 to 0.96; p = 0.0217)Sarcomatoid HistologyAll SarcmPFS: 8.3 vs. 5.3 (HR: 0.52; 0.34 to 0.79)PD-L1+ SarcmOS: 8.6 vs. 5.6 (HR: 0.45; 0.26 to 0.77)Gene Expression SignaturesHigh TeffmPFS: 12.45 vs. 8.34 (HR 0.76; 0.59–0.99)Low TeffmPFS: 9.72 vs. 8.41 mHigh angiogenesismPFS: 12.45 vs. 10.2 (HR 0.95; 0.75–1.19)Low angiogenesismPFS: 8.94 vs. 5.95 (HR 0.68; 0.52–0.89) | PD-L1¥ + (≥1%) dORR: 43% vs 35%Sarcomatoid HistologyAll SarcORR: 49% vs. 14%CR: 10 vs. 3%PD-L1+ SarcORR: 56% vs. 12%CR: 14% vs. 4% |
SH Sarcomatoid Histology
Cell population used: τ = tumor cells, ¥ = immune cells, β = both tumor and immune cells
Antibody used: a = Rabbit 28–8 (Dako), b = Mouse 22C3 (pharmDx), c = Rabbit SP263 (Ventana), d = Rabbit SP142 (Ventana)