Phase 1/2 dose escalation/expansion study of REGN10597 (anti–PD-1–IL2Rα-IL2) in patients with advanced solid tumors.

Abstract

TPS578 Background: Interleukin 2 (IL-2) is a cytokine involved in lymphocyte expansion and differentiation during the anticancer immune response. Despite clinical advances with checkpoint inhibitor therapies, many advanced solid tumors continue to respond poorly to these treatments. Aldesleukin, an approved recombinant high-dose IL-2 therapy, has shown complete and durable responses in some cases; however, high-dose IL-2 is associated with severe toxicity, including vascular leak syndrome and pulmonary edema. REGN10597 is an antibody–cytokine fusion protein comprising a human anti–programmed cell death-1 (PD-1) antibody fused with a receptor-masked cytokine, IL2Rα-IL2. REGN10597 has demonstrated tumor inhibition, enhanced specificity, and reduced toxicity versus recombinant high-dose IL-2 in preclinical mouse models (Wu et al. Cell Rep Med 2024). Here we describe a study evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of REGN10597 in patients with advanced solid tumors. Methods: This is an open-label, Phase 1/2, dose escalation/expansion, first-in-human, multicenter study evaluating REGN10597 in advanced or metastatic solid tumors (NCT06413680). Patients must be aged 18 years or over with histologically or cytologically confirmed locally advanced or metastatic tumors with confirmed disease progression on standard-of-care therapy. During the dose escalation phase, patients will be enrolled to receive REGN10597 by intravenous infusion at the assigned dose level and schedule (additional dose schedules are available for further exploration). When the recommended Phase 2 dose level and schedule is determined, additional patients will be enrolled across two dose expansion cohorts: patients with locally advanced or metastatic melanoma (Cohort 1) and those with advanced or metastatic clear cell renal cell carcinoma (Cohort 2). Dose escalation primary endpoints include incidence of dose-limiting toxicities, incidence of treatment-emergent adverse events (including those leading to treatment discontinuation or death), incidence of serious adverse events, and the number of patients with Grade ≥3 laboratory abnormalities. The dose expansion primary endpoint is objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment. Secondary endpoints for both phases include additional efficacy measures (best overall response, duration of response, disease control rate, time to response, and progression-free survival, all per RECIST v1.1), and pharmacokinetics and immunogenicity of REGN10597. Trial enrollment for the dose escalation phase began on October 1, 2024; as of October 21, 2025, 18 patients have been enrolled. Clinical trial information: NCT06413680 .