Table 4 Biomarker data reported with ICIs in advanced RCC

CheckMate 025

(NCT01668784)

[16]

Nivolumab vs. Everolimus

PD-L1 ^τ (< 1%) ^a

mOS: 27.4 vs. 21.2 mo (HR 0.77; 0.60 to 0.97)

PD-L1 ^τ (≥1%) ^a

mOS: 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%) ^a

HR 0.73; 95% CI, 0.56 to 0.96

12-mo rate: 80% vs. 75%

18-mo rate; 74% vs. 64%

PD-L1 ^τ (≥1%) ^a

HR 0.45; 0.29 to 0.71

12-mo rate: 86% vs. 66%

18-mo rate: 81% vs. 53%

Sarcomatoid Histology

HR 0.56; 0.38–0.83

PD-L1 (≥1%) prevalence: 50% (SH) vs. 27.5% (non-SH)

PD-L1 ^τ (< 1%) ^a

mPFS: 11.0 vs. 10.4 (HR 1.00; 0.8 to 1.26)

PD-L1 ^τ (≥1%) ^a

mPFS: 22.8 vs. 5.9 (HR 0.46; 0.31 to 0.67)

PD-L1 ^τ (< 1%) ^a

ORR: 37% vs. 28%, p = 0.03

PD-L1 ^τ (≥1%) ^a

ORR: 58% vs. 22%, p < 0.001

Sarcomatoid Histology

ORR: 56.7% vs. 19.2%, P < .0001

CR: 18.3% vs. 0%

Keynote-426

(NCT02853331)

[11] [insert ASCO abstract 4500]

Pembrolizumab + Axitinib vs. Sunitinib

PD-L1 ^β (< 1%) ^b

HR 0.59; 0.34 to 1.03

PD-L1 ^β (≥1%) ^b

HR 0.54; 0.35 to 0.84

Sarcomatoid Histology

12-mo OS: 83.4% vs 79.5% (HR 0.58; 0.21 to 1.59)

PD-L1 ^β (< 1%) ^b

HR 0.87; 0.62 to 1.23

PD-L1 ^β (≥1%) ^b

HR 0.62; 0.47 to 0.80

Sarcomatoid Histology

mPFS: NR vs. 8.4 (HR 0.54; 0.29 to 1.00)

Sarcomatoid Histology

ORR: 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%) ^c

mPFS: 13.8 vs 7.2 (HR 0.61; 0.47 to 0.79; P < 0.001)

PD-L1^¥- (< 1%) ^c

mPFS: 16.1 vs. 11.1

PD-L1^¥ + (≥1%) ^c

ORR: 55.2% vs 25.5%

CR: 4.4% vs. 2.1%

PD-L1^¥- (< 1%) ^c

ORR: 47% vs. 28%

IMmotion150

[46]

Atezolizumab + Bevacizumab or Atezolizumab monotherapy vs. Sunitinib

Not available.

ITT Population

Combination HR 1.0; 0.69 to 1.45

Monotherapy HR 1.19; 0.82 to 1.71

PD-L1^¥ + (≥1%) ^d

Combination HR 0.64; 0.38 to 1.08

Monotherapy HR 1.03; 0.63 to 1.67

PD-L1^¥ + (≥1%) ^d

48% (combination) and 28% (monotherapy) vs. 27%

IMmotion151

(NCT02420821)

[14] [insert ASCO abstract citation]

Atezolizumab + Bevacizumab vs. Sunitinib

PD-L1^¥ + (≥1%) ^d

OS: 75% vs. 65% (HR 0.68; 0.46–1.0; p = 0.0470)

Sarcomatoid Histology

All Sarc

mOS: NR vs. 15.0 (HR: 0.56; 0.32 to 0.96)

12-mo OS: 69% vs. 60%

PD-L1+ Sarc

mOS: NR vs. 15.0 (HR: 0.53; 0.27 to 1.06)

12-mo OS: 71% vs. 61%

PD-L1^¥ + (≥1%) ^d

mPFS: 11.2 vs. 7.7 (HR 0.74; 0.57 to 0.96; p = 0.0217)

Sarcomatoid Histology

All Sarc

mPFS: 8.3 vs. 5.3 (HR: 0.52; 0.34 to 0.79)

PD-L1+ Sarc

mOS: 8.6 vs. 5.6 (HR: 0.45; 0.26 to 0.77)

Gene Expression Signatures

High T_eff

mPFS: 12.45 vs. 8.34 (HR 0.76; 0.59–0.99)

Low T_eff

mPFS: 9.72 vs. 8.41 m

High angiogenesis

mPFS: 12.45 vs. 10.2 (HR 0.95; 0.75–1.19)

Low angiogenesis

mPFS: 8.94 vs. 5.95 (HR 0.68; 0.52–0.89)

PD-L1^¥ + (≥1%) ^d

ORR: 43% vs 35%

Sarcomatoid Histology

All Sarc

ORR: 49% vs. 14%

CR: 10 vs. 3%

PD-L1+ Sarc

ORR: 56% vs. 12%

CR: 14% vs. 4%