Subcutaneous Versus Intravenous Nivolumab in ccRCC: Results of the CheckMate 67T Trial

At the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium, Saby George, MD, FACP, presented results of the phase III CheckMate 67T study that compared the subcutaneous (SC) and intravenous (IV) delivery of nivolumab in patients with locally advanced or metastatic clear cell renal cell carcinoma (ccRCC).

While intravenous nivolumab has improved patient outcomes for multiple malignancies, there is a need for different administration options to address treatment burden and improve the efficiency of health care systems.

A total of 495 patients were enrolled and randomized 1:1 to receive nivolumab SC (n=248) 1200 mg with recombinant human hyaluronidase PH20 every 4 weeks, or nivolumab IV (n=247) 3 mg/kg every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, completion of 2 years’ treatment, or death. Eligible patients had measurable disease that progressed during or after 1-2 prior systemic regimens, no prior immuno-oncology treatment, and a Karnofsky performance score ≥ 70.

Pharmacokinetics (PK), efficacy, and safety were analyzed. The co-primary PK endpoints were time-averaged serum concentration over the first 28 days (Cavgd28) and minimum serum concentration at steady state (Cminss) determined by a population PK analysis. The key secondary endpoint was objective response rate (ORR), while other endpoints included safety, efficacy, and immunogenicity.

The average injection time with nivolumab SC was under 5 minutes. Noninferiority for the co-primary PK and key secondary ORR endpoints were met. The incidence of nivolumab SC local injection-site reactions was 8.1%, and reactions were low grade and transient. Most deaths were due to disease progression, while drug toxicity led to 3 deaths with nivolumab SC and 1 death from IV treatment.

With primary and key secondary endpoints met, nivolumab SC can be supported as a new treatment option for patients with ccRCC to improve healthcare efficiency, with a comparable safety profile to nivolumab IV.