. Author manuscript; available in PMC: 2017 Jul 28.

Published in final edited form as: Nat Rev Urol. 2016 Jun 21;13(7):420–431. doi: 10.1038/nrurol.2016.103

Table 1. Results of selected checkpoint blockade trials in patients with renal cell carcinoma.

Agent and trial	Phase	Population	Design	n	Response	Toxicities	Comments	Refs
Nivolumab (CheckMate 025)	III	Prior systemic therapies: 1: 72% 2: 28% MSKCC risk group: favourable: 36% intermediate: 49% poor: 15%	Open-label, 1:1 randomized trial	821	OS (months) nivolumab: 25 everolimus: 19 ORR nivolumab: 25% everolimus:5% PFS (months) nivolumab: 4.6 everolimus: 4.4	Grade 3–4 treatmentrelated AEs: nivolumab: 19% everolimus: 37%	Hazard ratio for death with nivolumab = 0.73 (P = 0.002)	37
Nivolumab and ipilimumab	I	Previously treated or treatmentnaive All MSKCC risk groups permitted	Randomized trial of three dosing cohorts: Induction Arm A: nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks × 4 Arm B: nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks × 4 Arm C: nivolumab 3 mg/kg ipilimumab 3 mg/kg every 3 weeks × 4 All followed by nivolumab 3mg/kg every 2 weeks until substantial disease progression or toxicity	100	ORR: Arm A: 38% Arm B: 40% PFS at 24 weeks: Arm A: 54% Arm B: 68% Median duration of response: Arm A: 67 weeks Arm B: 81 weeks	Treatment in Arm C stopped owing to toxicity Grade 3–4 treatment related AEs: Arm A: 34% Arm B: 64% Arm C: 83%	Median OS not reached with median follow-up duration ranging from 46–90 weeks	48
Atezolizumab and bevacizumab	Ib	Various solid tumours allowed For RCC prior systemic therapies: 0: 83% 1-2: 8% ≥3: 8%	Two arms: Arm A: atezolizumab and bevacizumab 15 mg/kg every 3 weeks Arm B: atezolizumab and bevacizumab 10 mg/kg every 2 weeks	13 RCC 71 total	ORR in RCC: 40% In total, 9 of 10 patients with RCC remained on treatment after median follow-up period of 7.8 months	Grade 3–4 AEs regardless of attribution across all tumour types: Arm A: 49% Arm B: 67% Grade 3–4 AEs attributed to atezolizumab across all tumour types: Arm A: 3% Arm B: 17%	Atezolizumab and bevacizumab 15 mg/kg every 3 weeks chosen as the dose for a phase 2 trial	62

Agent and trial

Phase

Population

Design

Response

Toxicities

Comments

Refs

Nivolumab (CheckMate 025)

III

Prior systemic therapies:

1: 72%
2: 28%

MSKCC risk group:

favourable: 36%
intermediate: 49%
poor: 15%

Open-label, 1:1 randomized trial

821

OS (months)

nivolumab: 25
everolimus: 19

ORR

nivolumab: 25%
everolimus:5%

PFS (months)

nivolumab: 4.6
everolimus: 4.4

Grade 3–4 treatmentrelated AEs:

nivolumab: 19%
everolimus: 37%

Hazard ratio for death with nivolumab = 0.73 (P = 0.002)

Nivolumab and ipilimumab

Previously treated or treatmentnaive
All MSKCC risk groups permitted

Randomized trial of three dosing cohorts:
Induction

Arm A: nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks × 4
Arm B: nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks × 4
Arm C: nivolumab 3 mg/kg ipilimumab 3 mg/kg every 3 weeks × 4

All followed by nivolumab 3mg/kg every 2 weeks until substantial disease progression or toxicity

100

ORR:

Arm A: 38%
Arm B: 40%

PFS at 24 weeks:

Arm A: 54%
Arm B: 68%

Median duration of response:

Arm A: 67 weeks
Arm B: 81 weeks

Treatment in Arm C stopped owing to toxicity
Grade 3–4 treatment related AEs:

Arm A: 34%
Arm B: 64%
Arm C: 83%

Median OS not reached with median follow-up duration ranging from 46–90 weeks

Atezolizumab and bevacizumab

Various solid tumours allowed
For RCC prior systemic therapies:

0: 83%
1-2: 8%
≥3: 8%

Two arms:

Arm A: atezolizumab and bevacizumab 15 mg/kg every 3 weeks
Arm B: atezolizumab and bevacizumab 10 mg/kg every 2 weeks

13 RCC
71 total

ORR in RCC: 40%
In total, 9 of 10 patients with RCC remained on treatment after median follow-up period of 7.8 months

Grade 3–4 AEs regardless of attribution across all tumour types:

Arm A: 49%
Arm B: 67%

Grade 3–4 AEs attributed to atezolizumab across all tumour types:

Arm A: 3%
Arm B: 17%

Atezolizumab and bevacizumab 15 mg/kg every 3 weeks chosen as the dose for a phase 2 trial

AE, adverse event; MSKCC, Memorial Sloan Kettering Cancer Center; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RCC, renal cell carcinoma.