Phase 3 Trial Results Support Subcutaneous Nivolumab Treatment for Patients With Metastatic ccRCC

The phase 3 CheckMate-67T trial (NCT04025879) evaluating subcutaneous nivolumab (Opdivo; Bristol Myers Squibb) co-formulated with a proprietary recombinant human hyaluronidase (rHuPH20) in patients with metastatic clear cell renal cell carcinoma (ccRCC) who received prior systemic therapy met its co-primary pharmacokinetics endpoints and key secondary endpoint. Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor that utilizes the body’s immune system to help restore anti-tumor immune response and is indicated for various types of cancers, such as unresectable or metastatic melanoma, non-small cell lung cancer, unresectable malignant pleural mesothelioma, advanced renal cell carcinoma, classical Hodgkin lymphoma, and urothelial carcinoma.

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CheckMate-67T is a randomized, open-label trial with a total of 495 patients with ccRCC who received prior systemic therapy who were randomized to receive either subcutaneous nivolumab or IV nivolumab.

The trial’s co-primary endpoints are time-averaged serum concentration over 28 days (Cavgd28) and trough serum concentration at steady-state (Cminss) of subcutaneous nivolumab compared to IV nivolumab. The secondary endpoint was objective response rate (ORR). Compared to the IV formulation, subcutaneous nivolumab had presented noninferiority of Cavgd28, Cminss, and ORR. The safety of the subcutaneous treatment was consistent with the IV formulation.

“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 healthcare systems. 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 [nivolumab],” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb.

Potential adverse effects (AEs) of nivolumab include immune-mediated pneumonitis, endocrinopathies (eg, thyroid disorders, adrenal insufficiency, hypophysis, diabetes), colitis, nephritis with renal dysfunction, hepatitis and hepatotoxicity, and dermatologic complications (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash). Nivolumab may also cause embryo-fetal toxicity in individuals who are pregnant and infusion-related AEs. Some serious AEs such as abdominal pain, hyponatremia, pneumonia, diarrhea, musculoskeletal pain, and acute kidney injury were reported by trial participants; however, the most common AEs were rash, constipation, vomiting, nausea, headache, upper respiratory tract infection.

Investigators expect to present CheckMate-67T trial results at an upcoming medical conference. Future trials will include additional research on secondary efficacy and safety endpoints.

“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,” said Fusaro.

Reference

Bristol Myers Squibb. 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. October 19, 2023. Accessed October 20, 2023. https://news.bms.com/news/corporate-financial/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