A First-In Human (FIH) Study to Find Out How Well REGN10597 Medicine Given Alone or in Combination With Cemiplimab Works in Adult Participants Who Have Cancer With Tumors That Have Spread in Their Body

Official title

A Phase 1/2a, Open-Label, Dose Escalation and Dose Expansion First-In-Human Study of the Safety, Tolerability, Activity, and Pharmacokinetics of REGN10597 (Anti-PD-1-IL-2RA-IL-2 Fusion Protein) Alone or in Combination With Cemiplimab in Patients With Advanced Solid Organ Malignancies

Overview

This study is researching an experimental drug called REGN10597 alone or in combination with another drug called cemiplimab (called "study drug(s)"). The study is focused on patients with certain solid tumors that are in an advanced stage. The aim of the study is to see how safe, tolerable, and effective the study drug(s) are. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug(s) * How much study drug(s) is in the blood at different times * Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)

Detailed description

Phase 1: Conducted in the United States only Phase 2: Conducted globally

Interventions

• Drug REGN10597
  Administered per the protocol
• Drug Cemiplimab
  Administered per the protocol

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: Up to Day 29]
• Incidence of Treatment-Emergent Adverse Event (TEAEs) [Time frame: Approximately 6 Years]
• Incidence of Serious Adverse Events (SAEs) [Time frame: Approximately 6 Years]
• Incidence of TEAEs leading to treatment discontinuation [Time frame: Approximately 6 Years]
• Incidence of TEAEs leading to death [Time frame: Approximately 6 Years]
• Number of participants with Grade 3 laboratory abnormalities [Time frame: Approximately 6 Years]
• Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria by investigator assessment [Time frame: Approximately 6 Years]

Secondary outcome measures (9)

• ORR based on RECIST 1.1 criteria by investigator assessment [Time frame: Approximately 6 Years]
• Best Overall Response (BOR) based on RECIST 1.1 criteria [Time frame: Approximately 6 Years]
• Duration Of Response (DOR) based on RECIST 1.1 criteria [Time frame: Approximately 6 Years]
• Disease control rate based on RECIST 1.1 [Time frame: Approximately 6 Years]
• Time to response based on RECIST 1.1 [Time frame: Approximately 6 Years]
• Progression Free Survival (PFS) based on RECIST 1.1 [Time frame: Approximately 6 Years]
• Concentrations of REGN10597 in serum [Time frame: Approximately 6 Years]
• Incidence of Anti-Drug Antibody (ADA) to REGN10597 over time [Time frame: Approximately 6 Years]
• Magnitude of ADA to REGN10597 over time [Time frame: Approximately 6 Years]

Eligibility criteria

Inclusion criteria

Dose escalation cohorts:

1\. Histologically or cytologically confirmed diagnosis of solid malignancy (locally advanced or metastatic) with confirmed progression on standard-of-care therapy. Participants are required to submit archival tissue if it is available

Dose expansion cohorts:

1\. Histologically of cytologically confirmed diagnosis of one of the following tumors with criteria, as defined in the protocol:

• Module 1, Cohort 1: anti-PD-(L)1 Progressed Melanoma or
• Module 1, Cohort 2: anti-PD-(L)1 Progressed RCC or
• Module 2, Cohort 1: 1L Melanoma ALL Participants ARE REQUIRED to submit fresh pretreatment biopsy during screening, with an additional exploratory biopsy at other time points

Exclusion criteria

• Prior treatment with Interleukin 2 (IL2)/IL15/IL-7 given outside the context of concurrent administration with adoptive cell therapy
• Prior treatment with anti-PD1/PD-L1, or an approved systemic therapy or any previous systemic non-immunomodulatory biologic therapy within 4 weeks, as defined in the protocol
• Has received radiation therapy or major surgery within 14 days prior to first dose of study drug or has not yet recovered from AEs
• Has had prior anti-cancer immunotherapy within 4 weeks prior to study intervention, or discontinuation of prior anti-cancer immunotherapy due to grade 3 or 4 toxicities
• Has ongoing immune-related AEs prior to initiation of study intervention, as defined in the protocol
• Has known allergy or hypersensitivity to components of the study drug(s)
• Has any condition requiring ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1-2 weeks to the first dose of study intervention
• Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments

NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• USC Norris Comprehensive Cancer Center — Los Angeles
• University of California San Francisco (UCSF) — San Francisco
• Yale School of Medicine — North Haven
• University of Chicago — Chicago
• Start Midwest Cancer Research — Grand Rapids
• Northwell Health — Lake Success
• University of North Carolina at Chapel Hill — Chapel Hill
• University of Pittsburgh Medical Center - Hillman Cancer Center — Pittsburgh
• … and 3 more centers

Identifiers

NCT: NCT06413680 · R10597-ONC-22114 · 2025-523399-22-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗