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FDA Approves Nivolumab and Hyaluronidase-nvhy for Subcutaneous Use in Patients With Solid Tumors
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Key Takeaways
- Nivolumab and hyaluronidase-nvhy is approved for subcutaneous use in adults with multiple solid tumors, offering a convenient alternative to intravenous administration.
- The CHECKMATE-67T trial demonstrated noninferiority in pharmacokinetic endpoints and a favorable safety profile for subcutaneous administration compared to intravenous nivolumab.
The approval offers patients with solid tumors an alternative to intravenous PD-1 inhibitor administration.
Nivolumab and hyaluronidase-nvhy (Opdivo Qvantig; Bristo, Myers Squibb) was approved by the FDA for subcutaneous injection across approved solid tumor nivolumab indications in adults as a monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy; Bristol Myers Squibb) combination therapy, or in combination with chemotherapy or cabozantinib (Cometriq; Exelixis, Inc). The approval, based on results from the CHECKMATE-67T trial (NCT04810078), 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.1,2
Nivolumab liquid in a vial | Image Credit: © uchschenF - stock.adobe.com
Nivolumab and hyaluronidase-nvhy is a programmed cell death protein-1 (PD-1) inhibitor co-formulated with recombinant human hyaluronidase (rHuPH20) meant for subcutaneous administration, allowing patients a more convenient and comfortable alternative to intravenous (IV) infusions.3
“This approval of subcutaneous nivolumab gives our patients a new option that can deliver consistent efficacy and comparable safety expected from IV nivolumab, and offers a patient-centric treatment experience,” said Professor Dr. Saby George, MD, FACP, medical oncologist and director of network clinical trials at Roswell Park Comprehensive Cancer Center.1 “[Nivolumab and hyaluronidase-nvhy] offers faster administration, delivered in 3 to 5 minutes. It may allow patients, in consultation with their doctors, to choose another treatment method and the flexibility to receive treatment closer to home.”3
The phase 3, randomized, open-label, noninferiority CHECKMATE-67T trial enrolled 495 adult patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC), who were randomized 1:1 to receive either 4 weeks of 1200 mg of subcutaneous nivolumab plus recombinant human hyalyronidase (n=248) or intravenous nivolumab at a dosage of 3 mg/kg (n=247) until disease progression, unacceptable toxicity, completion of treatment, or mortality. The coprimary pharmacokinetic end points were time-averaged concentration over 28 days (Cavgd28) and minimum concentration at steady state (Cminss). Overall response rate (ORR) was a key secondary end point.2-4
According to the study results, the trial met the coprimary end point, achieving the predefined acceptance criteria for pharmacokinetic end points, with the lower limit of the 90% confidence interval for geometric mean ratios meeting or exceeding 0.8 for both Cavgd28 over 28 days and Cminss. The trial also met its secondary end point of ORR. Of the patients receiving subcutaneous nivolumab and hyaluronidase-nvhy, there was a 24% ORR (95% CI: 19,30), compared with 18% (95% CI: 14, 24) in the intravenous nivolumab group.2,4
The safety profile of subcutaneous nivolumab and hyaluronidase-nvhy was favorable and consistent with the safety profile of IV nivolumab. Serious adverse effects occurred in 28% of patients receiving the subcutaneous treatment, the most common being pleural effusion (1.6%), pneumonitis (1.6%), hyperglycemia (1.2%), hyperkalemia (1.2%), hemorrhage (1.2%), and diarrhea (1.2%) in >1% of patients. The most common in ≥10% of patients were musculoskeletal pain (31%), fatigue (20%), pruritus (16%), rash (15%), hypothyroidism (12%), diarrhea (11%), cough (11%), and abdominal pain (10%). The incidence of local injection-site reactions was 8.1%.2-4
This approval marks a significant milestone as the first FDA-approved subcutaneous PD-1 inhibitor, offering a more convenient administration option without compromising efficacy. By expanding access to advanced immunotherapy, this breakthrough has the potential to enhance patient experiences and outcomes, underscoring its importance in the evolving landscape of cancer treatment.
