Subcutaneous Opdivo Similarly Effective, Safe as IV for Advanced ccRCC

Among patients with previously treated, advanced or metastatic clear cell renal cell carcinoma (ccRCC), subcutaneous Opdivo (nivolumab and hyaluronidase-nvhy, Opdivo Qvantig) was similarly effective, safe and tolerable when compared with intravenous (IV) Opdivo, clinical trial results have shown.

Updated results from the phase 3 CheckMate-67T clinical trial were presented during the 50th Annual Oncology Nursing Society Congress.

Results showed that at a minimum follow-up of 15 months, the overall response rate (ORR) was 27% for subcutaneous Opdivo (248 patients) versus 21% for IV Opdivo (247 patients). ORR was a key secondary end point powered for noninferiority. Notably, the study previously met its co-primary end points of time-averaged serum concentration over the first 28 days and minimum serum concentration at steady state during the primary analysis.

Additional data from the updated analysis showed that the median progression-free survival (PFS) was 6.3 months with subcutaneous Opdivo versus 5.7 months with the IV formulation. The median time to response was 3.7 months in both arms. Six- and 12-month overall survival (OS) rates were 84% and 72%, respectively, for subcutaneous Opdivo, compared with 86% and 73%, respectively, for IV Opdivo.

"CheckMate-67T met its co-primary end points and key powered secondary end point at the primary analysis, demonstrating pharmacokinetic and efficacy noninferiority of subcutaneous [Opdivo] to IV [Opdivo], " lead study author Daniel Adamczyk of Bristol Myers Squibb and colleagues wrote in a poster presentation of the data. "These data further support the use of subcutaneous [Opdivo] as a new option with reduced administration time to improve patient treatment experience and health care efficiency."

In December 2024, the FDA approved subcutaneous Opdivo for use across approved adult solid tumor IV Opdivo indications as monotherapy, as monotherapy maintenance following completion of Opdivo plus Yervoy (ipilimumab) combination therapy or in combination with chemotherapy or Cabometyx (cabozantinib). This regulatory decision was based on previously reported data from CheckMate-67T.

CheckMate-67T Design

CheckMate-67T evaluated the safety and efficacy of subcutaneous Opdivo compared with the standard IV formulation in patients with previously treated advanced or metastatic ccRCC. Eligible patients had experienced disease progression during or after at least one prior systemic regimen and had not previously received immuno-oncology therapy.

Enrolled patients were randomly assigned to receive either subcutaneous Opdivo at 1200 milligrams co-formulated with recombinant human hyaluronidase PH20 at 20,000 units every four weeks or IV Opdivo at 3 milligrams per kilogram every two weeks. Patients continued treatment until disease progression, unacceptable toxicity, withdrawal of consent, completion of two years of treatment, or death.

Beyond the co-primary pharmacokinetic end points and the key secondary end point of ORR, DOR, disease control rate, PFS and OS were other secondary end points assessed by blinded independent central review. Safety assessments included the incidence of side effects, treatment-related side effects, injection-site reactions and treatment discontinuations due to side effects or treatment-related side effects.

The study enrolled patients across 75 sites in 17 countries. Baseline characteristics and efficacy outcomes were evaluated in all randomized patients, while safety analyses included all patients who received at least one dose of Opdivo. Baseline patient demographics and disease characteristics were similar between the two arms.

Safety Analysis

Among patients treated with subcutaneous Opdivo (247 patients), any-grade side effects occurred in 93.1% of patients (grade 3, severe, or 4, life-threatening, 40.1%) compared with 94.3% (grade 3/4, 46.5%) for those given the IV formulation (245 patients). Treatment-related side effects of any grade were reported in 61.5% of patients in the subcutaneous arm, including 11.7% who experienced grade 3/4. Any-grade treatment-related side effects occurred in 65.7% of patients in the IV arm, including 17.1% who had grade 3/4.

Discontinuation due to any side effect occurred in 12.6% of patients in the subcutaneous arm, including 4.5% who discontinued treatment due to treatment-related side effects. These respective rates were 13.9% and 5.3% in the IV arm.

Immune-modulating medication was administered to 71.9% of patients who experienced an immune-mediated side effect in the IV arm (64 patients), and 32.8% of these patients received corticosteroids equivalent to at least 40 milligrams prednisone. These rates were 70.8% and 49.2%, respectively in the IV arm (65 patients).

Select any-grade treatment-related side effects in the subcutaneous Opdivo group included endocrine-related side effects at 12.6% (grade 3/4, 0.8%), gastrointestinal aide effects at 6.1% (1.2%), hepatic events at 9.3% (1.2%), pulmonary events at 4.9% (1.6%), renal events at 1.2% (0.4%), skin-related events at 24.3% (1.2%) and hypersensitivity or infusion reactions at 2.4% (0.4%).

In the IV group, any-grade treatment-related side effects included endocrine-related AEs at 18% (grade 3/4, 1.2%), gastrointestinal effects in 6.9% (0.4%), hepatic effects in 12.7% (1.2%), pulmonary effects in 3.3% (0.8%), renal effects in 2.4% (0.4%), skin-related effects in 27.3% (1.2%), and hypersensitivity or infusion reactions in 2.7% (0.4%).

Notably, treatment-related local injection site reactions (LISRs) were reported in 5% of patients in the subcutaneous arm versus 2% of patients in the IV arm. Five patients in the subcutaneous group needed intervention for LISRs, including four who received topical corticosteroids. All LISRs reported in the subcutaneous arm were grade 1, except for a single grade 2 occurrence.

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