Subcutaneous nivolumab may benefit patients across many indications

At the ASCO Genitourinary Cancers Symposium 2024, Dr Saby George, who is a professor of medical oncology at Roswell Park Cancer Institute, Buffalo, NY, USA, presented results from the CheckMate 67T trial [1]. This pharmacokinetic study compared subcutaneously versus intravenously administered nivolumab in patients with advanced kidney cancer. Medicom Medical Publishers interviewed Dr George to discuss the impact this trial will have on all cancer types that have nivolumab in their treatment arsenal.

Could you start by describing the CheckMate 67T trial?

“CheckMate 67T (NCT04810078) is a large, randomised, phase 3, open-label trial of subcutaneously administered nivolumab versus intravenously administered nivolumab in patients with advanced kidney cancer who had prior treatments,” said Dr George. “It was a pharmacokinetic study for non-inferiority, aiming to prove that subcutaneous administration of nivolumab is non-inferior to the traditional intravenous administration of nivolumab.”

In the trial, patients with advanced kidney cancer who had received 1 or 2 prior systemic treatments and no prior immunotherapy agents were stratified according to IMDC risk scores and baseline weight. Enrolled participants were randomised 1:1 to receive subcutaneous nivolumab at 1,200 mg along with rHuPH20 ( a reversible degrader of hyaluronic acid) every 4 weeks or intravenous nivolumab, 3 mg/kg every 2 weeks, which is the originally approved treatment from 2015. The co-primary pharmacokinetic endpoints were average serum concentration over 28 days and trough serum concentration at steady-state, and the key power secondary endpoint was objective response rate (ORR). Patients were enrolled across 17 countries and at 75 centres.

After a minimum follow-up of 8 months, the study met the co-primary endpoints for non-inferiority, meaning that subcutaneously administered nivolumab was non-inferior to intravenously administered nivolumab in terms of pharmacokinetics. “The secondary endpoint of ORR by blinded independent central review met the non-inferiority threshold as well and progression-free survival was 7.23 months in the subcutaneous arm and 5.65 months in the intravenous arm,” added Dr George. He also noted that the safety profiles of both treatment regimens were very comparable.

Importantly, nivolumab is approved for 22 different indications across many tumour types. This study is therefore impactful for many cancer treatments. “Testing the pharmacokinetic properties of subcutaneous nivolumab creates the rationale for using this approach in other diseases as well,” argued Dr George.

How will these results affect the day-to-day experience that patients have?

“Currently, nivolumab is administered over a period of approximately 30 minutes and patients occupy the chair for about 1 hour,” explained Dr George. “Subcutaneous nivolumab takes only 5 minutes to administer and needs to be given once every 4 weeks instead of once every 2 weeks. If subcutaneous nivolumab gets approved, the administration of nivolumab monotherapy could be moved from the infusion centre to the clinics. This would be especially helpful for people living in remote areas. In Buffalo, we have a lot of village-type areas and farmlands. People living in those areas are often overwhelmed to come to big cities. A nearby clinic would be a better option than an infusion centre in the city. Moreover, elderly patients don't always have a vehicle to travel to the city.”

What about the costs of subcutaneous versus intravenous administration?

“The pharmacokinetic values were non-inferior, but the subcutaneous dose was higher than the intravenous dose,” replied Dr George. “On the other hand, subcutaneous nivolumab is easier to administer. The cost may be determined by the manufacturer and the methodology of manufacturing. So I don’t know how it’s going to play out on that side of the equation. I can say another thing though: The infusion chair cost will also be reduced.”

Are there patients with other cancer types who may benefit from subcutaneous nivolumab administration?

“Since this was a pharmacokinetic study, the results apply to all the cancers in which nivolumab is used,” said Dr George. “Moreover, biosimilar compounds often get approved on pharmacokinetic studies alone, without needing phase 3 results. Here we have a large phase 3 trial with pharmacokinetics and ORR as endpoints. This is giving us a lot of confidence in saying that subcutaneous nivolumab works the way it should work. The safety, pharmacokinetics, progression-free survival, and response rates are all very similar to intravenous nivolumab. There should therefore be enough rationale to use this approach in all the other indications in which nivolumab is used as a single agent.

We haven’t tested the applicability of subcutaneous nivolumab in combination regimens, but since the pharmacokinetics are so similar to intravenous nivolumab it is likely to be feasible in combination therapy regimens as well,” Dr George continued. “Furthermore, other nivolumab studies did not reveal a dose-response relationship. Checkpoint inhibitors like nivolumab usually don't have a high ceiling dose,” he added. “Patients could have a response at a low dose or a high dose. They could have an adverse event at a low dose or a high dose. Therefore, subcutaneous nivolumab could be applicable in every indication. That's my opinion. But I will leave it up to the FDA to decide how this will be utilised.”

Finally, Dr George noted that subcutaneous nivolumab may be seen as an equity advantage. “Improving access is tied to disparities. So this is an opportunity to improve equity. And I think it should be optimally used to make it better for all the patients.”

1. George S et al, Subcutaneous Nivolumab Versus Intravenous Nivolumab in Patients With Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma: Pharmacokinetics, Efficacy, and Safety Results From CheckMate 67T. ASCO Genitourinary Symposium 2024, 24–27 January, San Francisco, CA, USA . J Clin Oncol.2024;42(suppl 4):LBA360.

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Posted on 17 July 2024