Clinical trial NCT06413680: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-05-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: Up to Day 28
measure: Incidence of treatment-emergent adverse event (TEAEs)
timeFrame: Approximately 6 Years
measure: Incidence of serious adverse events (SAEs)
timeFrame: Approximately 6 Years
measure: Incidence of TEAEs leading to treatment discontinuation
timeFrame: Approximately 6 Years
measure: Incidence of TEAEs leading to death
timeFrame: Approximately 6 Years
measure: Number of participants with Grade ≥3 laboratory abnormalities
timeFrame: Approximately 6 Years
measure: Objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST 1.1) criteria by investigator assessment
timeFrame: Approximately 6 Years
Secondary outcomes:
measure: ORR based on RECIST 1.1 criteria by investigator assessment
timeFrame: Approximately 6 Years
measure: Best overall response (BOR) based on RECIST 1.1 criteria
timeFrame: Approximately 6 Years
measure: Duration of response (DOR) based on RECIST 1.1 criteria
timeFrame: Approximately 6 Years
measure: Disease control rate based on RECIST 1.1
timeFrame: Approximately 6 Years
measure: Time to response based on RECIST 1.1
timeFrame: Approximately 6 Years
measure: Progression free survival (PFS) based on RECIST 1.1
timeFrame: Approximately 6 Years
measure: Concentrations of REGN10597 in serum
timeFrame: Approximately 6 Years
measure: Incidence of anti-drug antibody (ADA) to REGN10597 over time
timeFrame: Approximately 6 Years
measure: Titer of ADA to REGN10597 over time
timeFrame: Approximately 6 Years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: North Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Grand Rapids
country: United States
facility: Start Midwest Cancer Research
state: Michigan
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: San Antonio
country: United States
facility: The Start Center for Cancer Care
state: Texas
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: