FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors

Solid Tumor, Adult Clinical Trial

Official title:

A Phase I, Open-Label, Multicenter Study of FT538 in Combination With Monoclonal Antibodies in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05069935
• Other study ID #: FT538-102
• Status: Terminated
• Phase: Phase 1
• Start date: October 15, 2021
• Est. completion date: August 11, 2023

Study information

• Verified date: September 2023
• Source: Fate Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: August 11, 2023
• Est. primary completion date: August 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• FT538
FT538 is an allogeneic natural killer (NK)-cell immunotherapy
• Cyclophosphamide
Lympho-conditioning agent
• Fludarabine
Lympho-conditioning agent

Combination Product:
• Monoclonal antibody - Dose Escalation
either avelumab, trastuzumab or cetuximab
• Monoclonal antibody - Dose Expansion
either avelumab, atezolizumab, nivolumab, pembrolizumab, trastuzumab or cetuximab

Locations

Country	Name	City	State
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon	Nashville	Tennessee
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Define the Recommended Phase 2 Dose (RP2D)	To define the RP2D of FT538 in combination with the following mAbs in subjects with advanced solid tumors: avelumab, trastuzumab, cetuximab, atezolizumab, nivolumab, and pembrolizumab	Up to ~1.5 years
Primary	Incidence and Severity of Adverse Events (AEs)0	To evaluate the safety and tolerability of FT538 in combination with the following mAbs in subjects with advanced solid tumors: avelumab, trastuzumab, cetuximab, atezolizumab, nivolumab, and pembrolizumab	Up to ~5 years