In previously treated patients with advanced or metastatic clear cell renal cell carcinoma, a subcutaneous formulation of nivolumab was found to be noninferior to the intravenous formulation, which is standard of care for nivolumab in renal cell carcinoma and other cancers. Compared with intravenous nivolumab, subcutaneous nivolumab demonstrated noninferiority for the two co-primary pharmacokinetic endpoints and for secondary efficacy endpoints, including overall response rate. The safety of the two administration methods was generally similar, according to the results of the randomized, open-label, phase III CheckMate 67T trial, which were presented at the 2024 ASCO Genitourinary Cancers Symposium (Abstract LBA360).
“The equipoise of subcutaneous nivolumab and intravenous nivolumab is a groundbreaking advance for patients and physicians. Subcutaneous nivolumab is a new standard for clear cell renal cell carcinoma that will decrease treatment burden and improve health-care efficacy,” stated lead author Saby George, MD, of Roswell Park Comprehensive Cancer Center.
The average administration time for subcutaneous nivolumab was 5 minutes or less, compared with more than 30 minutes for intravenous nivolumab. This will “maximize efficiencies within health-care systems by freeing up infusion chairs, so we get more patients the medicine they need quickly,” Dr. George added. Further, he noted, the availability of a subcutaneous nivolumab option could improve access to care and reduce disparities for patients, since this method can be delivered in a clinic rather than an infusion center.
CheckMate 67T Details
In the study, patients with advanced or metastatic clear cell renal cell carcinoma who had received one or two prior systemic regimens were randomly assigned to receive subcutaneous nivolumab at 1,200 mg plus recombinant hyaluronidase every 4 weeks (n = 248) or intravenous nivolumab at 3 mg/kg every 2 weeks (n = 247).
The trial met the criteria for noninferiority with subcutaneous vs intravenous nivolumab, as well as for the co-primary pharmacokinetic endpoints of time-averaged serum concentration over 28 days and minimum serum concentration at steady state. Subcutaneous nivolumab was also noninferior to intravenous nivolumab for the secondary endpoint of objective response rate by blinded independent central review: 24.2% and 18.2%, respectively. Other secondary endpoints were similar with subcutaneous and intravenous nivolumab, including median time to response (3.7 vs 3.7 months, respectively) and median progression-free by blinded independent central review (7.2 vs 5.7 months, respectively).
“Antinivolumab antibodies were observed in a fraction of patients [on the subcutaneous formulation], but this did not result in a clinically meaningful impact on pharmacokinetics, efficacy, or safety,” Dr. George told listeners.
Safety was generally consistent between the two formulations of nivolumab. The overall rate of treatment-related adverse events was 59.1% (9.7% grade 3 or 4) with subcutaneous nivolumab and 64.5% (14.7% grade 3 or 4) with intravenous nivolumab.
Hypersensitivity reactions occurred in 1.2% and 3.7% of patients, respectively. Local-site reactions occurred in 8.1% vs 2%, respectively, and were reported to be transient. There were three deaths in the subcutaneous nivolumab arm and one in the intravenous arm, and none were attributed to treatment-related adverse events.
