FT825/ONO-8250, an Off-the-Shelf, HER2 CAR-T, With or Without Monoclonal Antibodies in Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor
• Interventions: Drug: FT825; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Bendamustine; Drug: Docetaxel; Drug: Cisplatin; Drug: Cetuximab

• Registration Number: NCT06241456
• Lead Sponsor: Fate Therapeutics

Brief Summary

This is a phase 1 study designed to evaluate the safety, tolerability, and antitumor activity of FT825 (also known as ONO-8250) with or without monoclonal antibody therapy following chemotherapy in participants with advanced human epidermal growth factor receptor 2 (HER2)-positive or other advanced solid tumors. The study will consist of a dose-escalation st...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study Start: 2024-01-05
• Study First Submitted: 2024-01-27
• Study First Submitted QC: 2024-01-27
• Study First Posted: 2024-02-05
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-22
• Last Update Posted: 2024-08-23
• Primary Completion: 2029-05-01
• Study Completion: 2044-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 351

Inclusion Criteria

• Histopathological or cytologically confirmed locally advanced or metastatic cancer that meets protocol-defined criteria
• Disease that is not amenable to curative therapy, with prior therapies defined by specific tumor types
• Contraceptive use by women and men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Presence of measurable disease by RECIST, v1.1 assessed within 28 days prior to start of first study intervention
• Anticipated life expectancy of at least 3 months

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Exclusion Criteria

• Females who are pregnant or breastfeeding
• Evidence of inadequate organ function
• Clinically significant cardiovascular disease
• Known active central nervous system (CNS) involvement by malignancy
• Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions within 2 years prior to study enrollment
• Active bacterial, fungal, or viral infections
• Prior receipt of chimeric antigen receptor (CAR) T-cell therapy, other cellular therapy, or a FATE investigational human induced pluripotent stem cell (iPSC) product
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out based on imaging at screening
• Any history of Grade ≥3 immune-related AE or Grade ≥2 eye toxicity attributed to prior cancer immunotherapy, other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase
• Active or history of autoimmune disease or immune deficiency
• Receipt of an allograft organ transplant

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen B: FT825 + Cetuximab	Cyclophosphamide	Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen B: FT825 + Cetuximab	Cisplatin	Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen B: FT825 + Cetuximab	Cetuximab	Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen B: FT825 + Cetuximab	FT825	Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen A: FT825	Cyclophosphamide	Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen A: FT825	Bendamustine	Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen A: FT825	FT825	Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen A: FT825	Fludarabine	Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen B: FT825 + Cetuximab	Bendamustine	Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen B: FT825 + Cetuximab	Docetaxel	Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen A: FT825	Docetaxel	Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen A: FT825	Cisplatin	Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
Regimen B: FT825 + Cetuximab	Fludarabine	Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).

Primary Outcome Measures

Name	Time	Method
Severity of AEs	Up to approximately 2 years	Severity of AEs will be determined according to appropriate rating scales for the type of event reported.
Number of participants with dose limiting toxicities (DLTs)	Up to approximately 29 days	The number of participants with DLTs will be reported.
Number of participants with treatment-emergent adverse events (TEAEs)	Up to approximately 2 years	The number of participants with TEAEs will be reported.

Secondary Outcome Measures

Name	Time	Method
Investigator-Assessed Duration of Response (DOR)	Up to approximately 2 years	DOR is the duration from the first occurrence of a documented objective response of either PR or CR until the time of disease progression, or death from any cause, whichever occurs first, per RECIST, v.1.1.
Investigator-Assessed Overall Response Rate (ORR)	Up to approximately 2 years	ORR is the proportion of participants who achieve partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST, v.1.1).
Progression-Free Survival (PFS)	Up to approximately 2 years	PFS is the time from first dose of study intervention to disease progression, or to the day of death for any reason, whichever occurs first, per RECIST, v.1.1.
Plasma Concentration of FT825	At designated time points up to approximately 56 days	The plasma concentration of FT825 will be determined.
Overall Survival (OS)	Up to approximately 2 years	OS defined as the time from first dose of study intervention to death from any cause.

Trial Locations

Locations (11)

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Ohio State University - Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Yale New Haven Hospital - Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of Minnesota Medical School; 🇺🇸 Minneapolis, Minnesota, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Oncology Hematology Care Clinial Trials; 🇺🇸 Cincinnati, Ohio, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute (SCRI) - Nashville; 🇺🇸 Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States