Phase 3 trial of subcutaneous nivolumab in ccRCC meets co-primary end points

The phase 3 CheckMate-67T trial (NCT04810078) exploring subcutaneous (SC) nivolumab (Opdivo) vs intravenous (IV) nivolumab in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior systemic therapy has met its co-primary pharmacokinetic end points.^1,2

Safety signals observed with SC nivolumab were consistent with those seen with IV nivolumab.

Data from the study showed noninferiority of SC nivolumab to IV nivolumab in the co-primary end points of time-average to nivolumab serum concentration over 28 days (Cavgd28) and the trough serum concentration at steady state (Cminss). The SC formulation also demonstrated noninferiority to IV nivolumab in the study’s key secondary end point of objective response rate (ORR) by Blinded Independent Central Review.

“Intravenous Opdivo 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,” commented Gina Fusaro, PhD, in a news release on the findings.¹ Fusaro is the vice president and global program lead of Bristol Myers Squibb, the developer of the therapy.

Fusaro continued, “We are delighted that the results of CheckMate -67T demonstrate that subcutaneous nivolumab delivers noninferior pharmacokinetics, in addition to objective response rate and safety data consistent with IV Opdivo. We believe this new option, given as a single injection administered in less than 5 minutes, could transform the treatment experience for both patients and physicians.”

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC. Patients were randomly assigned to receive a subcutaneous formulation of nivolumab with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20, Enhanze) or intravenous nivolumab.

Safety signals observed with SC nivolumab were consistent with those seen with IV nivolumab.

"We are pleased that the positive topline results from [Bristol Myers Squibb’s] trial of subcutaneous nivolumab with Enhanze support a shorter treatment time, as a single injection administered in less than 5 minutes, potentially making it a more convenient treatment option for patients," said Helen Torley, MB, ChB, MRCP, president and CEO of Halozyme Therapeutics, in a news release by the company.² "This is the fifth positive phase 3 data readout from our Wave 3 products in the [past] 19 months, supporting the high success rate in the translation of phase 1/2 Enhanze SC pharmacokinetic data into positive phase 3 data."

Patient follow-up for CheckMate-67T remains ongoing to assess additional secondary efficacy and safety end points. Bristol Myers Squibb plans to share the findings from the study at an upcoming medical meeting and discuss next steps for SC nivolumab with health authorities across multiple indications.

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. Published online and accessed October 19, 2023. https://www.businesswire.com/news/home/20231018115252/en/Phase-3-CheckMate--67T-Trial-of-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase-Meets-Co-Primary-Endpoints-in-Advanced-or-Metastatic-Clear-Cell-Renal-Cell-Carcinoma

2. Positive topline results reported from Bristol Myers Squibb’s phase 3 CheckMate-67T trial of subcutaneous nivolumab with Halozyme’s ENHANZE drug delivery technology for advanced or metastatic clear cell renal cell carcinoma. News release. Halozyme Therapeutics, Inc. Published online and accessed October 19, 2023. https://www.prnewswire.com/news-releases/positive-topline-results-reported-from-bristol-myers-squibbs-phase-3-checkmate-67t-trial-of-subcutaneous-nivolumab-with-halozymes-enhanze-drug-delivery-technology-for-advanced-or-metastatic-clear-cell-renal-cell-carcinoma-301961618.html

3. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. 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). Last updated October 12, 2023. Accessed October 19, 2023. https://clinicaltrials.gov/study/NCT04810078