AACR 2021: Combination Targeted Therapies Under Study in Resistant Kidney Cancer
Posted: Wednesday, April 14, 2021
In an attempt to improve outcomes for patients with advanced clear cell renal cell carcinoma whose disease progresses on PD-1/PD-L1 and VEGF inhibitors, Hans Hammers, MD, PhD, of the Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, and colleagues are turning their attention to an assortment of investigational immune and targeted combination therapies. Experimental combination arms will feature pembrolizumab plus the HIF-2a belzutifan (MK-6482), lenvatinib plus belzutifan, the co-formulation of the CTLA-4 inhibitor quavonlimab plus pembrolizumab (MK-1308A), the co-formulation of the LAB-3 inhibitor MK-4280 plus pembrolizumab (MK-4280A), and pembrolizumab plus the ILT4 inhibitor MK-4830. The study details were announced during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract CT243).
“This umbrella platform study is an open-label, rolling-arm, multicenter phase Ib/II trial in advanced clear cell renal cell carcinoma with an adaptive design that will evaluate safety and efficacy of experimental combinations of investigational agents targeting various mechanisms of action,” the investigators stated.
Eligible patients will have a histologically confirmed diagnosis of clear cell renal cell carcinoma and a Karnofsky Performance Scale score of at least 70; they also will have disease progression on or after treatment with a PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor. The study design includes a safety lead-in phase for experimental combinations without an established recommended phase II dose and then an efficacy phase. Primary study endpoints are safety and tolerability to establish a recommended phase II dose; co-primary endpoints of the efficacy phase are safety and objective response rate. Secondary endpoints of the efficacy phase are overall and progression-free survival, duration of response, and clinical benefit rate.
Disclosure: Dr. Hammers reported a relationship with Merck. For disclosures of the other study authors, visit abstractsonline.com.