Subcutaneous Nivolumab Meets PK and ORR End Points in Pretreated Advanced or Metastatic ccRCC

Treatment with subcutaneous nivolumab (Opdivo) co-formulated with recombinant human hyaluronidase (rHuPH20) demonstrated noninferior pharmacokinetics (PK) compared with intravenous (IV) nivolumab in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior systemic therapy, meeting the co-primary end points of the phase 3 CheckMate-67T trial (NCT04810078).¹

Specifically, subcutaneous nivolumab demonstrated noninferiority in time-averaged serum concentration over 28 days (Cavgd28) and trough serum at steady state (Cminns) vs IV nivolumab.

Additionally, data showed that patients treated with subcutaneous nivolumab experienced a noninferior objective response rate (ORR) compared with those treated with IV nivolumab per blinded independent central review assessment, meeting a key secondary end point of CheckMate-67T.

Safety data for subcutaneous nivolumab were also consistent with the known safety profile of the IV formulation.

Detailed findings from CheckMate-67T will be presented at an upcoming medical conference, and the drug’s developer, Bristol Myers Squibb, plans to discuss next steps for subcutaneous nivolumab with regulatory authorities.

“IV [nivolumab] has helped transform the treatment of several solid tumor types over the past decade, but there remains a need for additional administration options to address treatment burden on patients and improve efficiencies in health-care systems,” Gina Fusaro, PhD, vice president and global program lead at Bristol Myers Squibb, stated in a news release. “We are delighted that the results of CheckMate-67T demonstrate that subcutaneous nivolumab delivers noninferior PK, in addition to ORR and safety data consistent with IV [nivolumab]. We believe this new option, given as a single injection administered in less than five minutes, could transform the treatment experience for both patients and physicians.”

CheckMate-67T was a randomized, open-label study that enrolled patients at least 18 years of age with histologically confirmed, advanced or metastatic RCC with a clear cell component, including those with sarcomatoid features, whose disease was not amenable to curative surgery or radiation.² Key inclusion criteria included measurable disease per RECIST v1.1 criteria; no more than 2 prior lines of systemic therapy; intolerance to or progression on or after the last treatment regimen within 6 months of randomization; and a Karnofsky performance status of at least 70.

Patients were excluded if they had untreated, symptomatic central nervous system metastases; active, known, or suspected autoimmune disease; or any prior treatment with an anti–PD-1, anti–PD-L1, or anti–CTLA-4 antibody, or any other antibody or drug targeting T-cell co-stimulation or checkpoint pathways.

Investigators randomly assigned 495 patients to receive subcutaneous nivolumab or IV nivolumab.¹

Cavgd28 and Cminss served as the trial’s co-primary end points. Along with ORR, secondary end points included trough serum concentration at day 28, maximum serum concentration after the first dose, peak serum concentration at steady state, steady state average serum concentration, trough concentration, safety, disease control rate, duration of response, time to objective response, progression-free survival, and overall survival.²

References

1. Phase 3 CheckMate -67T trial of subcutaneous nivolumab (nivolumab and hyaluronidase) meets co-primary endpoints in advanced or metastatic clear cell renal cell carcinoma. News release. Bristol Myers Squibb. October 19, 2023. Accessed October 19, 2023. https://news.bms.com/news/details/2023/Phase-3-CheckMate--67T-Trial-of-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase-Meets-Co-Primary-Endpoints-in-Advanced-or-Metastatic-Clear-Cell-Renal-Cell-Carcinoma/default.aspx
2. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Updated October 12, 2023. Accessed October 19, 2023. https://www.clinicaltrials.gov/study/NCT04810078