FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors

NCT ID: NCT05069935

Last Updated: 2023-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-15

Study Completion Date

2023-08-11

Brief Summary

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

Detailed Description

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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.

Conditions

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Solid Tumor, Adult

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation

* 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)

Group Type EXPERIMENTAL

FT538

Intervention Type DRUG

FT538 is an allogeneic natural killer (NK)-cell immunotherapy

Cyclophosphamide

Intervention Type DRUG

Lympho-conditioning agent

Fludarabine

Intervention Type DRUG

Lympho-conditioning agent

Monoclonal antibody - Dose Escalation

Intervention Type COMBINATION_PRODUCT

either avelumab, trastuzumab or cetuximab

Dose Expansion

* 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

Group Type EXPERIMENTAL

FT538

Intervention Type DRUG

FT538 is an allogeneic natural killer (NK)-cell immunotherapy

Cyclophosphamide

Intervention Type DRUG

Lympho-conditioning agent

Fludarabine

Intervention Type DRUG

Lympho-conditioning agent

Monoclonal antibody - Dose Expansion

Intervention Type COMBINATION_PRODUCT

either avelumab, atezolizumab, nivolumab, pembrolizumab, trastuzumab or cetuximab

Interventions

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FT538

FT538 is an allogeneic natural killer (NK)-cell immunotherapy

Intervention Type DRUG

Cyclophosphamide

Lympho-conditioning agent

Intervention Type DRUG

Fludarabine

Lympho-conditioning agent

Intervention Type DRUG

Monoclonal antibody - Dose Escalation

either avelumab, trastuzumab or cetuximab

Intervention Type COMBINATION_PRODUCT

Monoclonal antibody - Dose Expansion

either avelumab, atezolizumab, nivolumab, pembrolizumab, trastuzumab or cetuximab

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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NK Cell Therapy Cy Flu mAb mAb

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fate Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fate Trial Disclosure

Role: STUDY_DIRECTOR

Fate Therapeutics

Locations

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Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Sarah Cannon

Nashville, Tennessee, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

NEXT Oncology

San Antonio, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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FT538-102

Identifier Type: -

Identifier Source: org_study_id

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