FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors

Fate Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor, Adult

Treatments: Drug: Cyclophosphamide; Combination Product: Monoclonal antibody - Dose Expansion; Drug: FT538; Combination Product: Monoclonal antibody - Dose Escalation; Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05069935

FT538-102

Details and patient eligibility

About

This is a Phase 1 dose-finding study of FT538 in combination with monoclonal antibodies.

Full description

This is a Phase 1 dose-finding study of FT538 given in combination with a monoclonal antibody following lymphodepletion in subjects with advanced solid tumors. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Subjects with locally advanced or metastatic disease who have progressed after at least one line of therapy and diagnosis of one of the following by treatment cohort:

• Cohort A: The following solid tumor malignancies where anti-PD-1/PD-L1 antibodies are approved: cutaneous melanoma, non-small cell/small cell lung cancer, renal cell carcinoma, head and neck squamous cell cancer, microsatellite instability-high/ mismatch repair deficient cancer, gastric cancer, esophageal cancer, cervical cancer, merkel cell carcinoma, endometrial carcinoma, tumor mutation burden-high ≥ 10 mutations/megabase], cutaneous squamous cell carcinoma, triple-negative breast cancer.
• Cohort B: HER2+ breast cancer that has relapsed or progressed on trastuzumab and progressed on either pertuzumab or HER2-targeting antibody drug conjugate; HER2+ gastric cancer that has relapsed or progressed on trastuzumab-containing therapy; OR any other HER2+ solid tumor having progressed on at least one line of standard-of-care therapy. For any tumor type in this cohort, HER2 status must be documented by a U.S. Food and Administration (FDA) approved test to be ≥2+ IHC or Average HER2 copy number ≥4 signals per cell by in situ hybridization.
• Cohort C: CRC having progressed following prior cetuximab treatment or has KRAS/NRAS mutation; HNSCC having progressed following prior cetuximab.

Capable of giving signed informed consent

Aged ~ 18 years old

Willingness to comply with study procedures and duration

Measurable disease per RECIST v1.1

For subjects with >1 measurable lesion by RECIST v1.1 that can be safely accessed, willingness to undergo tumor biopsy

Contraceptive use for women and men as defined in the protocol

Exclusion criteria

Pregnant or breast-feeding women

ECOG performance status greater than or equal to 2

Evidence of insufficient organ function

Clinically significant cardiovascular disease including left-ventricular ejection fraction < 45%

Receipt of therapy within 2 weeks prior to Day 1 or five half-lives, whichever is shorter or any investigational therapy within 28 days prior to Day 1

Known active central nervous system (CNS) involvement by malignancy that hasn'thas not remained stable for at least 3 months following effective treatment for CNS disease

Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis or neurodegenerative disease or receipt of medications for these conditions

Currently receiving or likely to require immunosuppressive therapy Active bacterial, fungal, or viral infections including hep B, Hep C or HIV Live vaccine within 6 weeks prior to start of lympho-conditioning

Known allergy to albumin (human) or DMSO

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

Dose Escalation

Experimental group

Description:

* Cohort A: FT538 plus avelumab in subjects with advanced solid tumors malignancies where anti-PD-1/PD-L1 antibodies are approved * Cohort B: FT538 plus trastuzumab in subjects with advanced documented HER2+ tumors * Cohort C: FT538 plus cetuximab in subjects with advanced colorectal cancer (CRC) or head and neck squamous cell carcinoma (HNSCC)

Treatment:

Drug: Fludarabine

Combination Product: Monoclonal antibody - Dose Escalation

Drug: FT538

Drug: Cyclophosphamide

Dose Expansion

Experimental group

Description:

* Cohort A, Arm 1: FT538 plus avelumab in subjects with advanced solid tumors malignancies where anti-PD-1/PD-L1 antibodies are approved (except urothelial carcinoma (UC)) * Cohort A, Arm 2: FT538 plus an anti-PD-1 antibody (nivolumab or pembrolizumab) in subjects with solid tumor malignancies where anti-PD-1/PD-L1 antibodies are approved (except UC) * Cohort B, Arm 1: FT538 plus trastuzumab in subjects with HER2+ tumors * Cohort C, Arm 1: FT538 plus cetuximab in subjects with advanced CRC or HNSCC Subjects with UC may be enrolled in the randomized expansion cohorts as follows: * Cohort A, Arm R1: FT538 plus avelumab * Cohort A, Arm R2: FT538 plus atezolizumab

Treatment:

Drug: Fludarabine

Combination Product: Monoclonal antibody - Dose Expansion

Drug: FT538

Drug: Cyclophosphamide