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 (BrILliance)

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

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)

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Advanced Solid Tumors; Clear-Cell Renal-Cell Carcinoma (ccRCC)
• Intervention / Treatment: Drug: Cemiplimab; Drug: REGN10597

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • Recruiting
      • USC Norris Comprehensive Cancer Center
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco (UCSF)
  • Connecticut
    • North Haven, Connecticut, United States, 06473
      • Recruiting
      • Yale School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • Start Midwest Cancer Research
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina at Chapel Hill
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center - Hillman Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • The START Center for Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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

Key Exclusion Criteria:

1. Prior treatment with Interleukin 2 (IL2)/IL15/IL-7 given outside the context of concurrent administration with adoptive cell therapy
2. 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
3. Has received radiation therapy or major surgery within 14 days prior to first dose of study drug or has not yet recovered from AEs
4. 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
5. Has ongoing immune-related AEs prior to initiation of study intervention, as defined in the protocol
6. Has known allergy or hypersensitivity to components of the study drug(s)
7. 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
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Monotherapy Dose Escalation; Multiple Dose Level (DL) Cohorts to identify the Recommended Phase 2 Dose (RP2D)	Drug: REGN10597; Administered per the protocol
Experimental: Phase 2: Monotherapy Dose Expansion; Cohort 1: Melanoma participants Cohort 2: Clear-cell Renal-Cell Carcinoma (ccRCC) participants	Drug: REGN10597; Administered per the protocol
Experimental: Phase 1: Combination Dose Escalation; Multiple DL Cohorts to identify the RP2D	Drug: Cemiplimab; Administered per the protocol; Drug: REGN10597; Administered per the protocol
Experimental: Phase 2: Combination Dose Expansion; Cohort 1: Melanoma participants	Drug: Cemiplimab; Administered per the protocol; Drug: REGN10597; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities (DLTs)	Dose escalation	Up to Day 29
Incidence of Treatment-Emergent Adverse Event (TEAEs)	Dose escalation	Approximately 6 Years
Incidence of Serious Adverse Events (SAEs)	Dose escalation	Approximately 6 Years
Incidence of TEAEs leading to treatment discontinuation	Dose escalation	Approximately 6 Years
Incidence of TEAEs leading to death	Dose escalation	Approximately 6 Years
Number of participants with Grade 3 laboratory abnormalities	Dose escalation Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Approximately 6 Years
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria by investigator assessment	Dose expansion	Approximately 6 Years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• BrILliance

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2024
• Primary Completion (Estimated): February 3, 2030
• Study Completion (Estimated): February 3, 2030

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic; Unresectable; Locally advanced; Advanced solid organ malignancies; Non-uveal; Primary or secondary resistance to programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1 (PD-L1)
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplastic Processes; Skin Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Carcinoma, Renal Cell; Melanoma; cemiplimab
• Other Study ID Numbers: R10597-ONC-22114; 2025-523399-22-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No