Bristol Myers Squibb announced that the U.S. Food and Drug Administration (FDA) granted approval for Opdivo Qvantig? (nivolumab and hyaluronidase-nvhy) injectionfor subcutaneous use, a combination product of nivolumabco-formulated with recombinant human hyaluronidase (rHuPH20), in most previously approved adult, solid tumor Opdivo indications as monotherapy, monotherapy maintenance following completion of Opdivo plus Yervoy® (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib. The approval is based on the results from the Phase 3 randomized, open-label CheckMate-67T trial, which demonstrated non-inferior co-primary pharmacokinetic (PK) exposures, similar efficacy in overall response rate (ORR), and showed a comparable safety profile vs.

intravenous (IV) Opdivo. In the trial, noninferiority was demonstrated for the co-primary endpoints of time-averaged concentration over 28 days (Cavgd28) and minimum concentration at steady state (Cminss) of Opdivo Qvantig vs. IV Opdivo.

The geometric mean ratios (GMRs) for Cavgd28 was 2.10 (90% CI: 2.00-2.20) and the GMR for Cminss was 1.77 (90% CI: 1.63-1.93). As a key powered secondary endpoint, the overall response rate (ORR) in the Opdivo Qvantig 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 Opdivo Qvantig has similar efficacy compared to IV Opdivo. Subcutaneous administration may offer flexibility to receive treatment where it is best for patients and their providers, and may reduce steps required for preparation and time needed for administration.5,6,7,8,9,10 In the CM?67T trial, average administration time with Opdivo Qvantig was approximately five minutes, and most patients received all doses of the study medication without an injection interruption or dose delay.

With this approval, Opdivo Qvantig is now the first and only subcutaneously administered PD-1 inhibitor, offering a faster delivery for patients to receive this immunotherapy treatment option in three to five minutes compared to 30-minute IV Opdivo. Opdivo and Opdivo Qvantig are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo or Opdivo Qvantig are added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials. Opdivo is associated with infusion related reactions.

About CheckMate-67T: CheckMate-67T was a Phase 3, randomized, open-label, noninferiority trial evaluating Opdivo Qvantig 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 Opdivo Qvantig (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 were time-averaged concentration over 28 days (Cavgd28) and minimum concentration at steady state (Cminss).

The key powered secondary endpoint was 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 Opdivo Qvantig (n=247). The most frequent serious adverse reactions reported in >1% of patients who received Opdivo Qvantig 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 Opdivo Qvantig (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 Opdivo Qvantig; these included myocarditis, myositis, and colitis complications. Study therapy was discontinued in 10% of patients due to adverse reactions.

The safety profile of Opdivo Qvantig was comparable with the safety profile of IV Opdivo. About Subcutaneous Administration: Subcutaneous administration is delivery of treatment beneath the skin and is an alternative to IV infusion.10 There are several potential benefits of subcutaneous administration: it may offer the flexibility to provide and receive treatment where it is best for the healthcare provider and patient, may impact infusion chair capacity, and may reduce time spent preparing and administering treatment. It may also simplify administering treatment for patients who have difficult-to-access veins or do not want a port.

Subcutaneous treatment has the potential to be administered by a healthcare professional without site of care restrictions.