A First-In Human (FIH) Trial to Find Out if REGN10597 is Safe and How Well it Works for Adult Participants With Advanced Solid Organ Malignancies

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-IL2RA-IL2 Fusion Protein) in Patients With Advanced Solid Organ Malignancies

This study is researching an experimental drug called REGN10597 (called "study drug"). 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 is.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma; Advanced Solid Tumors; Clear-Cell Renal-Cell Carcinoma (ccRCC)
• Intervention / Treatment: Drug: REGN10597

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

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

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 malignancy (locally advanced or metastatic) with confirmed progression on standard-of-care therapy
2. Participants are required to submit archival tissue with optional fresh biopsy

Dose-expansion cohorts:

1. Histologically of cytologically confirmed diagnosis of Melanoma or ccRCC tumors with criteria, as defined in the protocol
2. Participants are required to submit fresh pretreatment biopsy during screening

Key Exclusion Criteria:

1. Prior treatment with Interleukin 2 (IL2)/IL15/IL7
2. Prior treatment with anti PD-1/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 2 months prior to study therapy
5. Has ongoing immune-related AEs prior to initiation of study drug, as defined in the protocol
6. Has known allergy or hypersensitivity to components of the study drug
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 drug
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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose Escalation; Multiple dose level (DL) Cohorts to identify the recommended Phase 2 dose (RP2D)	Drug: REGN10597; Administered as an intravenous (IV) infusion
Experimental: Phase 2: Dose Expansion; Cohort 1: Melanoma Participants Cohort 2: Clear-cell renal-cell carcinoma (ccRCC) participants	Drug: REGN10597; Administered as an intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (DLTs)		Up to Day 28
Incidence of treatment-emergent adverse event (TEAEs)		Approximately 6 Years
Incidence of serious adverse events (SAEs)		Approximately 6 Years
Incidence of TEAEs leading to treatment discontinuation		Approximately 6 Years
Incidence of TEAEs leading to death		Approximately 6 Years
Number of participants with Grade ≥3 laboratory abnormalities	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
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
Disease control rate based on RECIST 1.1		Approximately 6 Years
Time to response based on RECIST 1.1		Approximately 6 Years
Progression free survival (PFS) based on RECIST 1.1		Approximately 6 Years
Concentrations of REGN10597 in serum		Approximately 6 Years
Incidence of anti-drug antibody (ADA) to REGN10597 over time		Approximately 6 Years
Titer of ADA to REGN10597 over time		Approximately 6 Years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): September 5, 2024
• Primary Completion (Estimated): March 21, 2030
• Study Completion (Estimated): March 21, 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): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2024
• Last Verified: May 1, 2024

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: Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: R10597-ONC-22114

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, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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