URO ONCO

Welcome, this website is intended for all international healthcare professionals in uro-oncology. By clicking the link below you are declaring and confirming that you are a healthcare professional.

You are here

Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC)

BJU Int. 2014 Oct;114(Suppl 4):2

Abstract

Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has clinical activity in mRCC. VEGF TKIs suppress regulatory T cells and myeloid-derived suppressor cells, making the immune environment more conducive for T-cell–mediated antitumor activity. Combining VEGF TKIs with positive immune modulation may result in greater/more durable therapeutic benefit. We report preliminary results of a phase I trial of nivolumab combined with sunitinib or pazopanib in mRCC.

Methods: mRCC patients received IV nivolumab plus sunitinib (50 mg, 4 weeks on/2 weeks off; arm S) or pazopanib (800 mg daily; arm P) until progression/unacceptable toxicity. Starting nivolumab dose was 2 mg/kg every 3 weeks (N2), with planned escalation to 5 mg/kg every 3 weeks (N5). Based on tolerability, arm S + N5 was expanded to treatment-naïve patients. Primary objectives were safety/tolerability and determination of maximum tolerated dose (MTD); secondary objective was antitumor activity.

Results: Seven patients each were treated in arms S + N2 and S + N5. No dose-limiting toxicities (DLTs) were observed and MTD was not reached; S + N5 was thus expanded by 19 patients. Four DLTs (elevated KCA 2014 CA209-016 sut/paz abstract_Final Submitted ALT/AST [n = 3], fatigue [n = 1]) were observed in P + N2 (n = 20 treated patients); this arm was therefore closed. Grade 3/4–related adverse events (AEs) were observed in 27/33 patients (82%) in arm S and 14/20 patients (70%) in arm P. Most common related grade 3/4 AEs were elevated ALT and hypertension (18% each) in arm S; and elevated ALT and AST, and diarrhea (20% each) in arm P. Grade 3 pneumonitis occurred in one patient (S + N5). Grade 3/4-related AEs led to discontinuation in 10/33 patients (30%) in arm S and 4/20 patients (20%) in arm P. Objective response rate (ORR) was 52% (17/33) and 45% (9/20), respectively. At 5% PD-L1 cutoff, ORR was 20% and 58.3% in PD-L1+ and PD-L1– patients, respectively, in arm S; and 50.0% and 46.7% in arm P. Responses occurred by first assessment (6 weeks) in 41% and 56% of patients, respectively. Duration of response range was 18.1–80 + and 12.1–90.1 + weeks, respectively. Progression-free survival rate at 24 weeks was 79% and 55%, respectively.

Conclusions: Nivolumab plus sunitinib showed encouraging antitumor activity and a manageable safety profile in mRCC patients. The pazopanib arm also showed encouraging antitumor activity but was closed due to DLTs. PD-L1 status did not appear to enrich for response.

Copyright © 1999-2015 John Wiley & Sons, Inc.

Comment from Henk van der Poel: Phase I study data: Nivolumab and sunitinib most attractive combination. Nivolumab and pazopanib resulted in dose-limiting toxicity in 20% of patients and seems less attractive.  Both combinations showed interesting response rates.

E-Alert

Subscribe to our E-Alert to keep up to date with the new items in the Resource Centre

Subscribe

URO ONCO is made possible by an unrestricted educational grant from:

The editorial independence of the resource centre is mandatory and recognized by the EAU and Elsevier.

The journal articles, videos and statements published on the resource centre have been selected independently and without influence from Elsevier, European Urology Editors or the sponsor and do not necessarily reflect their opinions or views.