A first-in-human phase I study of the PD-1 inhibitor, retifanlimab (INCMGA00012), in patients with advanced solid tumors (POD1UM-101)

Background: Retifanlimab is a humanized, hinge -stabilized immunoglobulin G4K monoclonal antibody against human programmed cell death protein 1 (PD -1). This first -in -human, phase I study assessed the safety and efficacy of retifanlimab in patients with advanced solid tumors and identified optimal dosing. Patients and methods: POD1UM-101 was conducted in two parts: (i) dose escalation -evaluated retifanlimab [1 mg/kg every 2 weeks (q2w), 3 or 10 mg/kg q2w or every 4 weeks (q4w)] in patients with relapsed/refractory, unresectable, locally advanced or metastatic solid tumors; (ii) cohort expansion-biomarker-unselected tumor -specific cohorts [endometrial, cervical, sarcoma, non -small -cell lung cancer (NSCLC)] received retifanlimab 3 mg/kg q2w, and tumoragnostic cohorts received flat dosing [375 mg every 3 weeks (q3w), or 500 and 750 mg q4w]. Primary objectives were safety and tolerability; secondary objective was efficacy in selected tumor types. Results: Thirty-seven patients were enrolled in dose escalation, 134 in PD -1 therapy -naive tumor -specific cohort expansion (endometrial, n 1/4 29; cervical, NSCLC, soft tissue sarcoma, each n 1/4 35), and 45 in flat dosing (375 mg q3w, 500 and 750 mg q4w, each n 1/4 15). No dose -limiting toxicities occurred during dose escalation; maximum tolerated dose was not reached and 3-mg/kg q2w expansion dose was selected based on safety and pharmacokinetic data. Immune -related adverse events were experienced by 40 patients (30%) in tumor -specific cohorts (most frequently hypothyroidism, hyperthyroidism, colitis, nephritis) and 6 (13%) in flat dosing (most frequently hypothyroidism, hyperthyroidism). Objective response rate (95% confidence interval) was 14% (4.8 to 30.3), 14% (3.9 to 31.7), 20% (8.4 to 36.9), and 3% (0.1 to 14.9) in advanced NSCLC, endometrial, cervical, and sarcoma tumor -specific cohorts that progressed after multiple prior systemic therapies. Conclusions: Retifanlimab demonstrated clinical pharmacology, safety, and antitumor activity consistent with the programmed death (ligand)-1 inhibitor class. POD1UM-101 results support further exploration of retifanlimab as monotherapy and backbone immunotherapy in combination treatments, with recommended doses of 500 mg q4w and 375 mg q3w.