SUMMARY: The FDA on December 27, 2024, approved Nivolumab and hyaluronidase-nvhy (OPDIVO Qvantig®) for subcutaneous injection across approved adult, solid tumor Nivolumab indications as monotherapy, monotherapy maintenance following completion of Nivolumab plus Ipilimumab (YERVOY®) combination therapy, or in combination with chemotherapy or Cabozantinib. The approval includes indications for renal cell carcinoma, melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma, esophageal carcinoma, gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. OPDIVO Qvantig® is not indicated in combination with intravenous Ipilimumab.
The American Cancer Society estimates that 81,610 new cases of kidney and renal pelvis cancers were diagnosed in the United States in 2024 and about 14,390 people died from the disease. Renal Cell Carcinoma (RCC) is by far the most common type of kidney cancer and is about twice as common in men as in women. Modifiable risk factors include smoking, obesity, workplace exposure to certain substances and high blood pressure. The five year survival of patients with advanced RCC is less than 10% and there is a significant unmet need for improved therapies for this disease.
OPDIVO® (Nivolumab) is a fully human, immunoglobulin G4 monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2. Blocking the Immune checkpoint proteins unleashes the T cells, resulting in T cell proliferation, activation, and a therapeutic response. The emergence of immunotherapy has offered new avenues for patients, with Nivolumab demonstrating efficacy across various tumor types. However, the conventional Intravenous (IV) administration of Nivolumab has been associated with significant treatment burden, prompting the exploration of alternative delivery methods. The CheckMate 67T trial aimed to address this challenge by assessing the efficacy and convenience of Subcutaneous (SC) Nivolumab compared to its IV counterpart.
The CheckMate 67T trial is an international, multicenter, randomized, open-label, Phase III study, conducted to evaluate the pharmacokinetics of Subcutaneous OPDIVO Qvantig® versus Intravenous delivery of Nivolumab in patients with locally advanced or metastatic clear cell Renal Cell Carcinoma (RCC). In this study, a total of 495 patients (N=495) were randomly assigned 1:1 to receive Nivolumab 1200 mg SC plus recombinant human hyaluronidase PH20 (OPDIVO Qvantig®) every 4 weeks (N=248), or Nivolumab 3 mg/kg IV every 2 weeks (N=247), until disease progression, unacceptable toxicity or completion of 2 years of treatment. The median age was 65 years, 67% were men and enrolled patients had measurable disease that progressed during or after 1–2 prior systemic regimens, had no prior immunotherapy treatment, and had a Karnofsky Performance Score of 70 or more. Hispanic patients accounted for at least 34% of study participants in both treatment arms, ensuring diverse representation.
The Primary objective of the study was to evaluate the pharmacokinetics of OPDIVO Qvantig® versus IV delivery of Nivolumab, which included whether blood levels of the drug were comparable in the two groups over time and whether OPDIVO Qvantig® was noninferior to IV Nivolumab. The daily average concentration of the drug in the blood over 28 days and the concentration of the drug at the end of the dosing cycle were measured. Key Secondary endpoint included Objective Response Rate (ORR) by Blinded Independent Central Review (BICR).
The trial revealed compelling findings, indicating that OPDIVO Qvantig® not only matched the pharmacokinetic profile (noninferior) and Objective Response Rate of IV Nivolumab, but also drastically reduced administration time. The ORR for the OPDIVO Qvantig® group was noninferior to the Intravenous group, at 24.2% versus 18.2%, respectively. The Median Progression Free Survival was 7.23 months for the OPDIVO Qvantig® group versus 5.65 months for the IV group. The median treatment duration was under 5 minutes for the OPDIVO Qvantig® group, in contrast to the 30-minute infusion sessions required for IV therapy. Local injection site reactions occurred in 8.1% of patients. Reactions were low grade and transient and most deaths were due to disease progression.
It was concluded that Subcutaneous OPDIVO Qvantig® showed comparable pharmacokinetic profile and Overall Response Rates (ORR) compared to Intravenous Nivolumab, in addition to significant reduction in administration time. With over 20 FDA-approved indications for Nivolumab, the convenience of Subcutaneous administration and its potential impact extends far beyond Renal Cell Carcinoma, promising greater accessibility and streamlined treatment experiences for patients nationwide. By alleviating treatment burdens and enhancing efficiency, this innovative formulation heralds a new era in oncology, offering hope to patients and clinicians alike.
Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. George S, Bourlon MT, Chacon MR, et al. Journal of Clinical Oncology. Volume 42, Number 4_suppl. https://doi.org/10.1200/JCO.2024.42.4_suppl.LBA360.
