Phase 1/2a Study of REGN10597 Alone or with Cemiplimab in Patients with Advanced Solid Tumours, Melanoma, or Clear-Cell Renal Cell Carcinoma

The primary objective of the first‑in‑human study is to evaluate the safety of REGN10597 administered alone and with cemiplimab during dose escalation and to assess preliminary anti‑tumor activity during dose expansion, providing early evidence of therapeutic benefit in advanced solid tumours such as melanoma, clear‑cell renal‑cell carcinoma, and other metastatic cancers. Secondary objectives include: – assessment of anti‑tumor activity in both escalation and expansion cohorts; – characterization of the pharmacokinetics of REGN10597 alone and in combination; – evaluation of the immunogenicity of REGN10597 alone and with cemiplimab.

The trial enrolled a total of 134 adult patients, inclusive of both female and male participants, who were diagnosed with solid malignancies such as Melanoma, advanced solid tumours, or clear‑cell renal‑cell carcinoma (ccRCC). Eligible individuals were required to be 18 years of age or older and to have histologically or cytologically confirmed locally advanced or metastatic disease with documented progression following standard‑of‑care therapy. Selection was based on the presence of the specified cancer diagnoses, with participants in the dose escalation cohorts providing archival tumour tissue when available, and those in the dose expansion cohorts required to undergo a fresh pretreatment biopsy and an additional exploratory biopsy at designated time points. General health status was limited to patients capable of undergoing study procedures; specific lifestyle factors such as diet, physical activity, or smoking habits were not stipulated in the provided information. Additional protocol‑defined inclusion and exclusion criteria applied but were not detailed in the source data.

The study is a Phase 1/2a, open‑label, first‑in‑human trial employing a dose‑escalation cohort followed by a dose‑expansion cohort to evaluate the safety, tolerability, pharmacokinetics and preliminary anti‑tumor activity of REGN10597 administered alone or in combination with cemiplimab in adults with advanced solid tumours, including melanoma and clear‑cell renal‑cell carcinoma. Participants undergo a screening visit to confirm eligibility, provide archival tissue (dose‑escalation) or a fresh pretreatment biopsy (dose‑expansion), and obtain baseline assessments. Subsequent treatment visits occur at regular intervals for intravenous infusion of the investigational product(s) and collection of safety laboratory data, pharmacokinetic samples, and imaging for response evaluation according to RECIST 1.1. Follow‑up visits continue at predefined time points after the last dose to monitor for delayed adverse events and disease status, concluding with an end‑of‑study visit. The overall participant involvement extends from the screening visit through the end‑of‑study assessment, with the trial recruitment period projected from June 2026 to April 2030. Early termination may occur if a participant experiences a dose‑limiting toxicity, a serious adverse event, disease progression, or fails to comply with protocol requirements, including withdrawal of consent.

The investigational anti‑PD‑1 monoclonal antibody cemiplimab is supplied as LIBTAYO 350 mg concentrate for solution for infusion, a sterile concentrate intended for reconstitution and administration by intravenous infusion. The product is given as an infusion on the treatment days defined by the dose‑escalation and dose‑expansion schedule of the protocol.

The fusion protein designated REGN10597 comprises an IgG4 antibody fragment targeting programmed cell death protein 1, fused to interleukin‑2 and an antibody fragment against the interleukin‑2 receptor α subunit. It is provided as a powder for solution for injection and is reconstituted for delivery by intravenous infusion according to the dose‑escalation schema, with each infusion administered on the protocol‑specified days.

No placebo or standard‑of‑care comparator is employed; participants receive either the investigational agent alone or in combination with cemiplimab as described. Compliance with the infusion schedule is monitored through infusion logs and drug accountability records at each study visit.

Efficacy will be evaluated using tumor response criteria, specifically the Objective Response Rate assessed according to RECIST 1.1 by investigator review. Additional efficacy parameters include Best Overall Response, Duration of Response, Disease control rate, Time to response, and Progression Free Survival, all derived from RECIST 1.1 assessments.

Response evaluations will be performed by qualified investigators using standardized imaging modalities at predefined study visits. Data will be collected, recorded, and analyzed in accordance with the RECIST 1.1 methodology to ensure consistency across participants and study sites.