## Protocol Section
### Identification Module
**NCT ID:** NCT06413680

**Brief Title:** 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

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

#### Organization Study ID Info
**ID:** R10597-ONC-22114
#### Organization
**Class:** INDUSTRY
**Full Name:** Regeneron Pharmaceuticals
### Status Module
#### Completion Date
**Date:** 2030-03-21

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2030-03-21

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Regeneron Pharmaceuticals

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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)

**Detailed Description:** Phase 1: Conducted in the United States Phase 2: Conducted globally

### Conditions Module

**Conditions:**

- Melanoma

- Clear-Cell Renal-Cell Carcinoma (ccRCC)

- Advanced Solid Tumors

**Keywords:**

- Advanced solid organ malignancies

- Locally advanced

- Metastatic

- Non-uveal

- Unresectable

- Primary or secondary resistance to programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1 (PD-L1)

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 150

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Multiple dose level (DL) Cohorts to identify the recommended Phase 2 dose (RP2D)

**Intervention Names:**

- Drug: REGN10597

**Label:** Phase 1: Dose Escalation

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Cohort 1: Melanoma Participants Cohort 2: Clear-cell renal-cell carcinoma (ccRCC) participants

**Intervention Names:**

- Drug: REGN10597

**Label:** Phase 2: Dose Expansion

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Phase 1: Dose Escalation

- Phase 2: Dose Expansion

**Description:** Administered as an intravenous (IV) infusion

**Name:** REGN10597

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Incidence of dose-limiting toxicities (DLTs)

**Time Frame:** Up to Day 28

**Measure:** Incidence of treatment-emergent adverse event (TEAEs)

**Time Frame:** Approximately 6 Years

**Measure:** Incidence of serious adverse events (SAEs)

**Time Frame:** Approximately 6 Years

**Measure:** Incidence of TEAEs leading to treatment discontinuation

**Time Frame:** Approximately 6 Years

**Measure:** Incidence of TEAEs leading to death

**Time Frame:** Approximately 6 Years

**Description:** Grade 3 or higher per Common terminology criteria for adverse events (CTCAE) version 5.0

**Measure:** Number of participants with Grade ≥3 laboratory abnormalities

**Time Frame:** Approximately 6 Years

**Description:** Dose-expansion

**Measure:** Objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST 1.1) criteria by investigator assessment

**Time Frame:** Approximately 6 Years

#### Secondary Outcomes

**Description:** Dose-escalation

**Measure:** ORR based on RECIST 1.1 criteria by investigator assessment

**Time Frame:** Approximately 6 Years

**Measure:** Best overall response (BOR) based on RECIST 1.1 criteria

**Time Frame:** Approximately 6 Years

**Measure:** Duration of response (DOR) based on RECIST 1.1 criteria

**Time Frame:** Approximately 6 Years

**Measure:** Disease control rate based on RECIST 1.1

**Time Frame:** Approximately 6 Years

**Measure:** Time to response based on RECIST 1.1

**Time Frame:** Approximately 6 Years

**Measure:** Progression free survival (PFS) based on RECIST 1.1

**Time Frame:** Approximately 6 Years

**Measure:** Concentrations of REGN10597 in serum

**Time Frame:** Approximately 6 Years

**Measure:** Incidence of anti-drug antibody (ADA) to REGN10597 over time

**Time Frame:** Approximately 6 Years

**Measure:** Titer of ADA to REGN10597 over time

**Time Frame:** Approximately 6 Years

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** clinicaltrials@regeneron.com

**Name:** Clinical Trials Administrator

**Phone:** 844-734-6643

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Regeneron Pharmaceuticals

**Name:** Clinical Trial Management

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**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

**Description:** All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

- ANALYTIC_CODE

**IPD Sharing:** YES

**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.

**URL:** https://vivli.org/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000002277

- Term: Carcinoma

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000007680

- Term: Kidney Neoplasms

- ID: D000014571

- Term: Urologic Neoplasms

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000007674

- Term: Kidney Diseases

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12307

- Name: Neoplasm Metastasis

- Relevance: LOW

- As Found: Unknown

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M11528

- Name: Melanoma

- Relevance: LOW

- As Found: Unknown

- ID: M5548

- Name: Carcinoma, Renal Cell

- Relevance: HIGH

- As Found: Clear Cell Renal Cell Carcinoma

- ID: M6845

- Name: Death

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M10703

- Name: Kidney Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17320

- Name: Urologic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M10698

- Name: Kidney Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4906

- Name: Renal Cell Carcinoma

- Relevance: HIGH

- As Found: Renal Cell Carcinoma

- ID: T1341

- Name: Clear Cell Renal Cell Carcinoma

- Relevance: HIGH

- As Found: Clear Cell Renal Cell Carcinoma

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

- ID: D000002292

- Term: Carcinoma, Renal Cell

### Misc Info Module

- Version Holder: 2024-05-31
