Subcutaneous Nivolumab Preferred Over IV for ccRCC: PROs From CheckMate 67T

The open-label, phase 3 CheckMate 67T trial compared the pharmacokinetics and objective response rate (ORR) noninferiority of subcutaneous (SC) nivolumab against intravenous (IV) nivolumab in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC).

María T. Bourlon, MD, MSc, presented new results of the study focused on additional safety analyses and patient-reported outcomes (PROs) at the 2024 American Society of Clinical Oncology Annual Meeting.

The multicenter, randomized study involved 495 patients. SC nivolumab 1200 mg with recombinant human hyaluronidase PH20 was administered every 4 weeks to 248 patients, while IV nivolumab 3 mg/kg every 2 weeks was administered to 247.

Initial results met the noninferiority end points of exposure (time-averaged serum concentration over the first 28 days and trough serum concentration at steady state) and efficacy (ORR by blinded independent central review). Safety was similar in both the SC and IV treatment arms, and nivolumab-related immunogenicity was as expected for SC administration.

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). Researchers examined the onset, management, and resolution of treatment-related select AEs. The 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 GP5.

In the SC arm, overall AE incidence rates were comparable with or lower than the rates in the IV arm across all weight categories, but results were limited by small sample sizes in the <50 kg and ≥110 kg subgroups.

In the treatment-related select AE categories, most events were manageable and resolved with immune-modulating treatments. Local site reactions were mild to moderate, with a median duration of 2.00 and 0.01 days in the SC and IV arms, respectively; most resolved without treatment.

Local site reactions of any grade occurred in 8.1% of patients in the SC arm and 2.0% in the IV arm. In patients testing nivolumab-specific anti-drug antibody (ADA)-positive, 15.2% of patients in the SC arm reported grade 1 or 2 local site reactions, but most resolved without treatment.

No hypersensitivity- or infusion reaction-related AEs were reported in the ADA-positive patients in either treatment arm. Analyses based on weight and ADA subgroups were consistent with the known safety profile of nivolumab, and toxicity was manageable with immune-modulating medication.

The majority of patients in both the SC and IV arms reported minimal bother from treatment side effects. With a safety profile comparable with IV administration, SC nivolumab is supported as an option that can improve patient experience, aligning with patient preference of SC administration over IV.