A subcutaneous (SC) form of nivolumab was just as effective as IV nivolumab on progression-free survival (PFS) in patients with previously treated advanced renal cell carcinoma (ccRCC), with no increase in hypersensitivity reactions. The SC form is more convenient and less time consuming to administer, with an average administration time of 5 minutes or less. These were the findings from the CheckMate 67T study presented by lead investigator Saby George, MD, at the 2024 ASCO Genitourinary Cancers Symposium.
“SC nivolumab is likely comparable to IV nivolumab, and has potential to make therapy more convenient and easier tolerated,” said Dr George, from Roswell Park Comprehensive Cancer Center, Buffalo, NY. “The results are groundbreaking in terms of overall patient experience, which includes reducing treatment burden, improving access, reducing the cost of treatment delivery, and reducing the wait time for infusion chairs. If approved by the US Food and Drug Administration, this treatment has the potential to reduce disparities in cancer care.”
Evolving treatment paradigms require administration options that decrease treatment burden for patients and improve the efficiency of healthcare systems, said Dr George. He said SC delivery of antibodies for various cancer indications has already proved to be effective and well tolerated, adding that “SC administration is typically preferred to IV infusion by patients and has improved healthcare resource utilization by decreasing preparation and chair occupancy time as well as reducing administrative burden.”
CheckMate 67T is a multicenter, randomized, open-label, phase 3 study that evaluated pharmacokinetic (PK) and response noninferiority of nivolumab SC versus IV in 495 patients with locally advanced or metastatic ccRCC treated in the second- or third-line setting. Patients with advanced or metastatic ccRCC that progressed during or after 1 to 2 prior systemic regimens were randomized to 1200 mg of SC nivolumab plus recombinant human hyalurondinase PH20 every 4 weeks or IV nivolumab, 3 mg/kg every 2 weeks, until disease progression, unacceptable toxicity, withdrawal of consent, completions of 2 years of treatment, or death. The 1200-mg dose of SC nivolumab chosen for this study was selected based on a dose-finding phase 1/2 study. Patients were enrolled across 73 sites in 17 countries. Minimum follow-up was 8 months. About 90% of patients in each arm had received 1 prior line of therapy, and >80% had prior nephrectomy. At baseline, central nervous system metastasis was present in 13.7% of the SC arm and 9.3% of the IV arm.
The average administration time of SC nivolumab was a mean of 4.7 minutes, compared with a mean of 30.9 minutes for IV nivolumab. Most patients received all doses of the study medications without an infusion/injection interruption or dose delay. Some 36.0% in the SC arm and 54.7% in the IV arm had at least 1 dose delayed, and 0.4% versus 4.1%, respectively, had at least 1 infusion or injection interrupted. The most common reason for dose delays of treatment was adverse events. Median PFS was similar between the two arms, at 7.23 months in the subcutaneous arm and 5.65 months in the IV arm.
The safety profile of SC nivolumab was consistent with the safety profile of IV nivolumab with no new safety concerns or signals identified. Local site reactions with SC nivolumab were low grade, transient, and most resolved without treatment, and no increase in hypersensitivity reactions or the risk of anaphylaxis was observed. The rate of development of antidrug antibodies was higher with SC nivolumab versus IV (22.8% vs 7.0%). “That [difference] apparently did not have any clinically meaningful impact on PK efficacy or safety,” he said.
“These data indicate that NIVO SC [SC nivolumab] provides clinical equipoise to standard IV dosing, supporting the use of SC nivolumab as a new option to reduce patients’ treatment burden and improve healthcare efficiency,” said Dr George.