ASCO 2017: Phase 3 KEYNOTE-426 trial: Pembrolizumab (pembro) plus axitinib versus sunitinib alone in treatment-naive advanced/metastatic renal cell carcinoma (mRCC)

Chicago, IL (UroToday.com) In this exciting era of checkpoint inhibitor therapy, combination studies have emerged in first-line clinical trials for advanced treatment-naïve renal cell carcinoma (RCC). At this morning’s ASCO 2017 genitourinary cancer poster session, Dr. Rini and colleagues presented their trial design for KEYNOTE-426, a phase III study assessing pembrolizumab + axitinib vs sunitinib alone in patients with advanced RCC who are treatment-naïve. A phase Ib study (n=52) suggests first-line pembrolizumab, an anti–programmed death 1 antibody, in combination with axitinib, has substantial antitumor activity in mRCC (objective response rate [ORR] 71%) and manageable side effects.

For this study, key eligibility criteria included (i) age ≥18 years, (ii) histologically confirmed mRCC with clear cell component (with or without sarcomatoid features), (iii) measurable disease (RECIST v1.1), (iv) no prior systemic therapy for advanced disease, (v) Karnofsky performance status ≥70%, and (vi) provision of a tumor sample for biomarker analyses. Patients will be stratified by IMDC risk category and geographic region, and approximately 840 patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg every 3 weeks + axitinib 5 mg twice daily or sunitinib 50 mg once daily for 4 weeks followed by 2 weeks off. Treatment will continue until progressive disease, unacceptable adverse events, or withdrawal of consent. Notably, patients in the pembrolizumab arm may receive up to 35 doses of medication, after which axitinib-only treatment may continue. Primary end points are to compare progression-free survival (RECIST v1.1) and overall survival between treatment arms. Secondary end points include the (i) ORR, (ii) duration of response, (iii) disease control rate, safety, and (iv) patient-reported outcomes between arms. Abdominal imaging will be performed at week 12, then every 6 weeks for the first year, and every 12 weeks thereafter. Bone scans will be performed at baseline, and if positive, repeated at week 18, 30, 42, and 54, and every 24 weeks thereafter. This study has started enrolling patients in 16 countries worldwide and is currently ongoing.
Clinical trial: NCT02853331

Presented By: Brian I. Rini, Cleveland Clinic, Cleveland, OH, USA

Co-Authors: Thomas Powles, Mei Chen, Markus Puhlmann, Michael B. Atkins

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA

References:
1. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015 Nov 5;373(19):1803-1813.
2. Haas NB, Manola J, Uzzo RB, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): A double-blind, placebo-controlled, randomized, phase III trial. Lancet 2016 May 14;387(10032):2008-2016.
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