A phase I study evaluating subcutaneous administration of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced solid malignancies

PURPOSE: Pharmacokinetics, pharmacodynamics, safety, and efficacy of subcutaneous cetrelimab were assessed in Parts (P)3 and 4 of the phase I LUC1001 study in patients with advanced/refractory solid tumors who progressed on or wereineligible for standard treatment and had no prior PD-1/PD-L1/PD-L2 treatment. METHODS: In P3, low-concentration cetrelimab (30 mg/mL) was administered subcutaneously at 600 mg with a 6-week interval between doses 1 and 2, then every 3 weeks (Q3W). Based on P3 pharmacokinetic and safety findings, high-concentration cetrelimab (150 mg/mL) was administered subcutaneously at a 900 mg loading dose followed by 600 mg Q3W in P4. RESULTS: Among 30 enrolled patients (P3, n = 11; P4, n = 19), median age was 54.5y; 76.7% received ≥ 3 prior lines of therapy. Median duration of treatment was 2.1mo. Treatment-related adverse events (AEs) occurred in 70% of patients, including 23.3% with grade ≥ 3 treatment-related AEs and 30.0% immune-related AEs; no treatment-related serious AEs or systemic infusion-related reactions occurred. After 3.7mo median follow-up, 2 patients (6.7%) achieved durable responses and 4 patients (13.3%) had stable disease for ≥ 24 weeks. Pharmacokinetic data showed that adding a 900 mg loading dose to the 600 mg Q3W subcutaneous regimen shortened the time to reach target recommended phase 2 dose (RP2D) exposures, making it a suitable intravenous alternative. Maximum PD-1 receptor occupancy was achieved with both formulations. Anti-cetrelimab antibodies were detected in 4 patients (13.3%); none were neutralizing. CONCLUSIONS: RP2D of subcutaneous cetrelimab was established as a loading dose of 900 mg followed by 600 mg Q3W. Subcutaneous cetrelimab demonstrated characteristics consistent with prior characterization of intravenous cetrelimab. Trial registration NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016-002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.