Coordinated Pembrolizumab and High Dose IL-2 (5-in-a-Row Schedule) for Therapy of Metastatic Clear Cell Renal Cancer.

The ligation of the interleukin-2 (IL-2) receptor and immune checkpoint blockade may each alter lymphocytes, thereby inducing regression in various cancers. Single agent objective response rates of 14% to 25% have been reported for usual schedule 14-dose-in-a-row IL-2 therapy of metastatic clear cell renal cancer (ccRCC), with a notable subset of responses being durable. Pembrolizumab yielded a 33% response rate in patients with metastatic ccRCC.

This study addressed the safety and feasibility of the combination of IL-2 and pembrolizumab in the treatment of metastatic ccRCC. Subjects were treated with four 9-week blocks of therapy, receiving pembrolizumab every 3 weeks in all blocks and receiving 4 courses of 5-planned-doses high dose IL-2 in each of blocks 2 and 3. Safety was monitored by a Pocock boundary of study suspension and re-evaluation if exceeding a 15% dose limiting toxicity rate at α = 0.05. The Simon 2-stage design tested for an alternative hypothesis response rate of at least a 45% vs. a null hypothesis rate of less than 20%, with α = 0.10 and 90% power RESULTS: No accrual suspension for safety was triggered. The objective response rate was 70% (19/27, 95% CI: 0.50-0.86). Nine patients responded after pembrolizumab alone and ten responded after the addition of IL-2. At a minimum follow-up of 23 months, 9 of the responding patients had no disease progression requiring additional treatment.

The combination of 5-planned-dose-schedule high dose IL-2 and pembrolizumab is feasible, with a high response rate, justifying further exploration of this dual immune treatment of metastatic ccRCC.

Clinical genitourinary cancer. 2022 Feb 09 [Epub ahead of print]

Jonathan Chatzkel, Michael J Schell, Jad Chahoud, Jingsong Zhang, Rohit Jain, Jennifer Swank, Steve Ludlow, Kristina Lombardi, Yesenia Lucas, Cortlin Croft, Jennifer Rembisz, Gigi Jameel, Mayer Fishman

Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, FL., H. Lee Moffitt Cancer Center, Department of Biostatistics and Bioinformatics, Tampa, FL., H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL; University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL., H. Lee Moffitt Cancer Center, Department of Pharmacy, Tampa, FL., H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL., University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL; Tampa General Hospital Cancer Institute, Genitourinary Oncology, Tampa, FL. Electronic address: .