FDA Approves Subcutaneous Injection of Nivolumab, Hyaluronidase-nvhy for NSCLC, Other Solid Tumor Indications

The US Food and Drug Administration (FDA) has approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig, Bristol Myers Squibb Company) for subcutaneous injection across most previously approved nivolumab indications for adults with solid tumors, including non-small cell lung cancer (NSCLC).

These indications include using the treatment as a monotherapy, a monotherapy maintenance after completion of nivolumab plus ipilimumab combination therapy, or in combination with chemotherapy or cabozantinib. However, nivolumab and hyaluronidase-nvhy is not indicated in combination with intravenous ipilimumab.

In addition to NSCLC, the approval for subcutaneous injection includes indications for renal cell carcinoma, melanoma, head and neck squamous cell carcinoma, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma, esophageal carcinoma, gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

The approval of nivolumab and hyaluronidase-nvhy makes it the “first and only subcutaneously administered PD-1 inhibitor,” officials from Bristol Myers Squibb said in a news release.

“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,” Saby George, MD, FACP, medical oncologist and director of network clinical trials at Roswell Park Comprehensive Cancer Center, said in a statement provided by Bristol Myers Squibb. “Opdivo Qvantig offers faster administration, delivered in three to five minutes. It may allow patients, in consultation with their doctors, to choose another treatment method and the flexibility to receive treatment closer to home.”

The approval is based on the results from the phase 3 CheckMate-67T trial, which “demonstrated non-inferior co-primary pharmacokinetic exposures, similar efficacy in overall response rate (ORR), and showed a comparable safety profile versus intravenous Opdivo,” according to Bristol Myers Squibb.

CHECKMATE-67T Data on Subcutaneous Nivolumab, Hyaluronidase-nvhy

The open-label CHECKMATE 67T trial evaluated the subcutaneous injection of nivolumab and hyaluronidase-nvhy at multiple centers. The study comprised 495 patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received no more than two prior systemic treatment regimens. The study investigators randomized patients to receive subcutaneous nivolumab and hyaluronidase-nvhy or intravenous nivolumab.

The subcutaneous injection of nivolumab and hyaluronidase-nvhy was evaluated in CHECKMATE-67T (NCT04810078), a multicenter, randomized, open-label trial in patients with advanced or metastatic ccRCC who received no more than two prior systemic treatment regimens.

The primary objective of CHECKMATE-67T was to evaluate nivolumab exposure with subcutaneous administration compared to intravenous nivolumab. The key secondary objective of was to evaluate the overall response rate (ORR), as assessed by blinded independent central review. A total of 495 patients were randomized to receive either subcutaneous nivolumab and hyaluronidase-nvhy or intravenous nivolumab.

According to the FDA, the trial “met the predefined acceptance margin for pharmacokinetic endpoints, with the lower boundary of 90% confidence interval of geometric mean ratios of not less than 0.8 for both serum nivolumab C_avg over 28 days and C^min at steady state.”

The ORR was 24% (95% CI, 19-30) in patients receiving subcutaneous nivolumab and hyaluronidase-nvhy and was 18% (95% CI: 14, 24) in those receiving intravenous nivolumab.

“In general, CHECKMATE-67T showed a similar safety profile between OPDIVO QVANTIG and intravenous nivolumab,” FDA officials explained in the announcement, noting that the most common adverse reactions (≥10%) were fatigue, musculoskeletal pain, pruritus, rash, and cough.

Recommended Dosage of Nivolumab and Hyaluronidase-nvhy for Subcutaneous Injection

According to the FDA, the recommended dosage of nivolumab and hyaluronidase-nvhy depends on the specific indication and is one of the following:

• Nivolumab 600 mg and 10,000 units of hyaluronidase every two weeks
• Nivolumab 900 mg and 15,000 units of hyaluronidase every three weeks
• Nivolumab 1,200 mg and 20,000 units hyaluronidase every four weeks until disease progression, unacceptable toxicity, or as indicated in the prescribing information.

Sources: FDA, Bristol Myers Squibb