CheckMate 67T: Subcutaneous Nivolumab for Advanced or Metastatic Clear Cell RCC

Saby George, MD, FACP, Roswell Park Comprehensive Cancer Center, provides details on his CheckMate 67T research into the potential utility of subcutaneous nivolumab for advanced or metastatic clear cell kidney cancer, including how this modality compares to traditional IV nivolumab, how to maintain rigorous lab monitoring with this approach, how it will be received by community practitioners, and ways it can improve healthcare inefficiency.

View Dr. George’s continued comments on the CheckMate 214 study.

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What’s the reasoning behind testing subcutaneous nivolumab rather than IV nivolumab with CheckMate 67T?

Dr. George: Intravenous nivolumab is approved for 22 different indications and is currently administered intravenously once every 4 weeks. However, nivolumab was approved for kidney cancer in 2015 based on CheckMate 025, using a 2-week schedule. Initially, it was administered at a dosage of 3 mg/kg of body weight. Subsequently, it evolved to a flat dose of 240 mg every 2 weeks and later to 480 mg every 2 weeks intravenously.

The rationale for testing subcutaneous administration is primarily based on enhancing convenience and potentially reducing the treatment burden on patients and healthcare systems. Subcutaneous administration offers advantages such as quicker delivery, elimination of the need for IV access or port, and a reduced risk of complications like port infections and extravasation. Generally, patients prefer subcutaneous administration, leading to the development of the nivolumab sub-Q formulation.

What does the data tell us about survival data for subcutaneous versus IV nivolumab?

Dr. George: The results indicate that the co-primary endpoints for non-inferiority were met. Both the C average day 28 and C minimum steady-state showed values above 0.8 within the lower band of the 95% confidence interval, rendering the study positive. Furthermore, the key powered secondary endpoint of objective response rate was 24.2% for subcutaneous administration and 18.2% for intravenous administration, meeting the non-inferiority threshold.

Additional secondary endpoints revealed that the median time to response was 3.7 months in both arms, and the median progression-free survival was 7.23 months in the subcutaneous arm and 5.65 months in the intravenous arm, indicating similarity between them. Immunogenicity analysis showed a higher ADA positivity in the subcutaneous arm (22.8%) compared to the intravenous arm (7%), but this did not impact PK efficacy or safety in further analyses.

Regarding safety, local site reactions were observed in the subcutaneous arm, but they were transient and resolved without treatment. The adverse event profile of subcutaneous nivolumab was similar to that of the intravenous form, indicating comparable safety. Importantly, the median administration time for subcutaneous nivolumab was less than 5 minutes, while for IV nivolumab, it was 30 minutes, significantly shorter.

Inherent in this treatment modality approach are the challenges of monitoring patients on their treatment plans, blood parameters, liver parameters, labs, etc. How do you propose maintaining the rigor of lab monitoring?

Dr. George: Adverse event management should continue similarly to how it is done for IV administration. Despite the different routes of administration, subcutaneous and IV nivolumab utilize the same compound and exhibit similar side effects. As the goal of nivolumab treatment is to activate T cells, which may cause toxicity when acting against normal tissue, monitoring must persist regardless of administration route.

How do you anticipate this potential standard-of-care option will be received by community practitioners?

Dr. George: Subcutaneously administered treatment offers several advantages over IV treatment. It eliminates the need for infusion centers, reducing patient inconvenience, avoiding the need for infusion chair bookings, and eliminating wait times associated with additional appointments. Additionally, it obviates the need for intravenous access, port placement, and complications related to intravenous administration, making it an attractive option for community oncology practices.

Your presentation highlighted the opportunity to use subcutaneous nivolumab in this setting to improve healthcare efficiency. How can this formulation improve healthcare inefficiency?

Dr. George: Implementing subcutaneous nivolumab can significantly improve healthcare efficiency. By transferring nivolumab administrations from infusion centers to outpatient clinics, it can alleviate the burden on infusion centers, reduce wait times for patients, and free up infusion chairs. For example, in our center, transitioning single-agent nivolumab administrations to the subcutaneous route could free up nearly 20 hours of chair time per week, thus expediting treatment for other patients. Additionally, reducing paperwork associated with scheduling separate appointments for clinic visits, lab work, and infusion treatments streamlines administrative processes, further enhancing efficiency.