Opdivo Subcutaneous Formulation Approved

Nivolumab for subcutaneous use co-formulated with recombinant human hyaluronidase (rHuPH20),(Opdivo Qvantig) is indicated across multiple previously approved adult solid tumors as monotherapy, monotherapy maintenance following completion of nivolumab plus Yervoy (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib. The CHMP opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines in the European Union (EU).

“The positive CHMP opinion is an important step forward in the evolution of immuno-oncology and in the potential of subcutaneous nivolumab to help transform the lives of people living with cancer,” said Dana Walker, M.D., M.S.C.E., Opdivo global program lead, Bristol Myers Squibb. “We look forward to bringing the same high-quality care that transformed cancer treatment with an administration method that has the potential to improve the patient experience and efficiency of healthcare systems in Europe."

The positive CHMP opinion is based on results from the CheckMate -67T trial, and additional data that demonstrated comparable pharmacokinetics and safety profiles between subcutaneous use of Opdivo and IV Opdivo , in which subcutaneous Opdivo demonstrated noninferiority of C avgd28 (time-averaged Opdivo serum concentration over 28 days) and C minss (trough serum concentration at steady state), the study’s primary endpoints, vs. intravenous (IV) Opdivo in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received no more than two prior lines of systemic therapy. The geometric mean ratio (GMR) for C avgd28 was 2.10 (90% CI: 2.00-2.20) and the GMR for C minss was 1.77 (90% CI: 1.63-1.93). Additionally, as a key powered secondary endpoint, the objective response rate (ORR) in the subcutaneous Opdivo arm (n=248) was 24% (95% CI: 19-30), compared with 18% (95% CI: 14-24) in the IV Opdivo arm (n=247), showing that subcutaneous Opdivo has similar efficacy compared to IV Opdivo . The safety profile of subcutaneous Opdivo was consistent with the IV formulation. The pharmacokinetics, efficacy and safety results from CheckMate -67T were presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Additional safety analyses and patient reported outcomes were presented at the 2024 ASCO Annual Meeting and the European Society for Medical Oncology (ESMO) Congress.

In the EU, the EC delivers its final decision within approximately two months following receipt of the CHMP opinion. Once issued, the decision will be applicable to all EU member states as well as in the European Economic Area (EEA) countries Iceland, Norway and Liechtenstein.

CheckMate -67T is a Phase III, randomized, open-label, noninferiority trial evaluating subcutaneous administration of Opdivo co-formulated with Halozyme’s proprietary recombinant human hyaluronidase rHuPH20, or subcutaneous nivolumab compared to intravenous (IV) Opdivo , in adult patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior systemic therapy. A total of 495 patients were randomized to receive either subcutaneous nivolumab (1,200 mg of nivolumab and 20,000 units of hyaluronidase) every 4 weeks subcutaneously (n = 248), or Opdivo 3 mg/kg every 2 weeks intravenously (n = 247). The coprimary endpoints are time-averaged concentration over 28 days (C avgd28 ) and minimum concentration at steady state (C minss ). The key powered secondary endpoint is overall response rate, as assessed by blinded independent central review.

Select Safety Profile from CheckMate -67T - Serious adverse reactions occurred in 28% of patients receiving subcutaneous nivolumab (n=247). The most frequent serious adverse reactions reported in >1% of patients who received subcutaneous nivolumab were pleural effusion (1.6%), pneumonitis (1.6%), hyperglycemia (1.2%), hyperkalemia (1.2%), hemorrhage (1.2%) and diarrhea (1.2%). The most common adverse reactions (≥10%) in patients treated with subcutaneous nivolumab (n=247) were musculoskeletal pain (31%), fatigue (20%), pruritus (16%), rash (15%), hypothyroidism (12%), diarrhea (11%), cough (11%), and abdominal pain (10%). Fatal adverse reactions occurred in 3 (1.2%) patients who received subcutaneous nivolumab; these included myocarditis, myositis, and colitis complications. Study therapy was discontinued in 10% of patients due to adverse reactions. The safety profile of subcutaneous nivolumab was comparable with the safety profile of IV Opdivo .