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

Fate Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Cetuximab; Drug: Bendamustine; Drug: Cisplatin; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: FT825; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT06241456

FT825-101

Details and patient eligibility

About

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 stage, followed by an expansion stage to further evaluate the safety and activity of FT825 in indication-specific cohorts.

Enrollment: 351 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

351 participants in 2 patient groups

Regimen A: FT825

Experimental group

Description:

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).

Treatment:

Drug: Docetaxel

Drug: FT825

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Cisplatin

Drug: Bendamustine

Regimen B: FT825 + Cetuximab

Experimental group

Description:

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).

Treatment:

Drug: Docetaxel

Drug: FT825

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Cisplatin

Drug: Cetuximab

Drug: Bendamustine