Subcutaneous (SC) nivolumab (NIVO) vs intravenous (IV) NIVO in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Safety and patient-reported outcomes (PROs) of the randomized phase 3 CheckMate 67T trial.

Abstract

4532 Background: CheckMate 67T (NCT04810078), a multicenter, randomized, open-label, phase 3 study, evaluated pharmacokinetics and objective response rate (ORR) noninferiority of NIVO SC vs IV in previously treated patients with advanced/metastatic ccRCC. Noninferiority endpoints of exposure (time-averaged serum concentration over the first 28 days and trough serum concentration at steady state) and efficacy (ORR by BICR) were met. Safety was comparable in the SC vs IV arms. NIVO-related immunogenicity was as expected for SC administration and further assessments did not identify apparent clinically meaningful impact. This report focuses on additional safety analyses and PROs. Methods: Patients were randomized 1:1 to NIVO SC 1200 mg + recombinant human hyaluronidase PH20 Q4W (n = 248) or NIVO IV 3 mg/kg Q2W (n = 247). Eligibility criteria were previously reported. Safety analyses were performed for all-causality adverse events (AEs) across weight categories (< 50 kg, ≥ 50 kg–< 70 kg, ≥ 70–< 90 kg, ≥ 90 kg–< 110 kg, and ≥ 110 kg). The onset, management, and resolution of treatment-related select AEs were studied; duration and grade of local site reactions and the effect of immunogenicity on local site reactions were reported. PROs were assessed using the Functional Assessment of Chronic Illness Therapy (FACIT) GP5 item. Results: The overall AE incidence rates in the SC arm were generally comparable to or lower than in the IV arm across weight categories, but limited by small sample sizes in the < 50 kg and ≥110 kg subgroups. Across the treatment-related select AE categories, most events were manageable with established algorithms and resolved with immune-modulating medications. Local site reactions were mild to moderate with a median duration of 2.0 and 0.01 days in the SC and the IV arms, respectively; most resolved without treatment. The proportion of patients with a local site reaction of any grade was 8.1% in the SC arm and 2.0% in the IV arm. In patients testing NIVO-specific anti-drug antibody (ADA)-positive, 15.2% of patients in the SC arm reported a local site reaction, but all were grade 1–2 and most resolved without treatment. No hypersensitivity/infusion reaction select AEs were reported in ADA-positive patients in either arm. A majority of patients in SC and IV arms reported minimal bother by treatment side effects in their FACIT GP5 scores. Conclusions: The safety profile of SC was consistent with IV, supporting the use of NIVO SC as an option improving patient experience. This aligns with patient preference for SC administration over IV. Analyses based on weight and ADA subgroups were consistent with the known NIVO safety profile. Toxicity was manageable with immune-modulating medications. FACIT GP5 scores indicated no bother by treatment side effects. Clinical trial information: NCT04810078 .