Axitinib in combination with pembrolizumab in patients (pts) with advanced renal cell carcinoma (aRCC): Preliminary safety and efficacy results

Background

Axitinib, an inhibitor of vascular endothelial growth factor receptors, is approved for 2nd-line treatment of aRCC. Pembrolizumab is a humanized monoclonal antibody that blocks binding of the immune-checkpoint receptor programmed death-1 (PD-1) to its ligands (PD-L1/2). Here we report preliminary safety and efficacy results from an ongoing phase Ib study of axitinib plus pembrolizumab in treatment-naïve pts with aRCC.

Methods

Pts included have clear-cell aRCC with primary tumor resected, ≥1 measureable lesion, ECOG performance status 0-1, controlled hypertension, and no prior systemic therapy for aRCC. Axitinib is administered orally 5 mg twice daily; pembrolizumab is administered 2 mg/kg intravenously on Day 1 of each 3-week cycle. Tumors are assessed, using RECIST v1.1, at baseline, week 12, and every 6 weeks thereafter. Study endpoints include adverse events (AEs), other safety measures and tumor response. IHC-based assay was used to stain tumor cells for PD-L1 expression.

Results

As of March 1, 2016, 52 pts (79% male; 87% white; mean age 61 years) were enrolled. Eleven (21.2%) pts discontinued both treatments: disease progression (n = 4); treatment-emergent AEs (n = 6; diarrhea, headache/joint pain, fatigue/joint pain, colitis/hepatitis, aggravated rheumatoid arthritis/psoriasis, and drug-induced liver injury); and other (n = 1). Thirty-five (67.3%) pts had objective response: 2 had complete response and 33 had partial responses; 11 pts had stable disease. For the 11 pts enrolled in the dose finding phase, 7 remained progression free at 11 months and the median PFS is not yet mature. Ten pts tested positive for PD-L1. Most common (>2 pts) grade 3 AEs included hypertension (n = 10), diarrhea, headache, hyponatraemia, alanine aminotransferase (ALT) increased, and aspartate aminotransferase (AST) increased (n = 3 each). Grade 4 AEs included dyspnea and hyperuricaemia (n = 1 each). Immune-related ≥grade 3 AEs included ALT and AST (n = 2 each), and diarrhea and colitis (n = 1 each).

Conclusions

This preliminary analysis indicates axitinib plus pembrolizumab is well tolerated and exhibits antitumor activity in treatment-naïve pts with aRCC.

Clinical trial identification

NCT02133742

Legal entity responsible for the study

Pfizer Inc

Funding

Pfizer Inc

Disclosure

M.B. Atkins: declares receiving fees for consulting BMS, Pfizer, Novartis, Genentech-Roche, Merck, Amgen, Nektar, Eisai, AstraZeneca, GlaxoSmithKline, Peleton, and Acceleron. E.R. Plimack: consulting fees from Merck, GlaxoSmithKline, Pfizer, Bristol-Myers SquibbNovartis, Acceleron and Genentech/Roche, and grant support to her institution from Bristol-Myers Squibb, AstraZeneca, Peloton, Merck, GlaxoSmithKline, Acceleron, and Pfizer. M.N. Fishman: research funding from Amgen, Altor Biosciences, AstraZeneca, Aveo, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, GlaxoSmithKline, Merck, and Pfizer; speakers bureaus from Bayer, Exelixis, GlaxoSmithKline, Novartis, Pfizer, and Prometheus. D. McDermott: declares receiving fees for consulting BMS, Pfizer, Novartis, Genentech-Roche, Merck, and Exelixis. D.C. Cho: declares receiving fees for consulting from Pfizer, Genentech, Prometheus, Bristol-Meyers Squibb, and Exelixis. U. Vaishampayan: Consulting, honoraria and research support from Pfizer Inc and research support from Merck Inc. S. George: fees for consulting and advisory boards from Pfizer, Exelixis, Bristol-Myers Squibb, Novartis, Bayer, Sanofi-Aventis, Astellas, Xcenda, and Onclive, and grant support from Bristol-Myers Squibb, Novartis, Bayer, Pfizer, Acceleron, Merck, and Agensys. J. Tarazi: an employee of and own stock in Pfizer. B. Rosbrook: an employee of and own stock in Pfizer. K. Fernandez: an employee of and own stock in Pfizer. S. Keefe: an employee of Merck & Co., Inc. T. Choueiri: fees for consulting, advisory boards: GSK, Novartis, Pfizer, Merck, AstraZeneca, Bayer, Prometheus; grant support through his institution: Bristol-Myers Squibb, GSK, Novartis, Exelixis, Pfizer, Merck, Roche, AstraZeneca, TRACON, Peloton. All other authors have declared no conflicts of interest.