FT536 Monotherapy and in Combination With Monoclonal Antibodies in Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase I, Open-Label, Multicenter Study of FT536 as Monotherapy and in Combination With Monoclonal Antibodies in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05395052
• Other study ID #: FT536-101
• Status: Terminated
• Phase: Phase 1
• Start date: May 31, 2022
• 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 FT536 given in combination with a monoclonal antibody following lymphodepletion in participants 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: 5
• 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:

• Participants with locally advanced or metastatic disease who have progressed/relapsed, are refractory, intolerant to or refuse standard therapy approved for their specific tumor type: Cohort A/A2/AA/AA2: NSCLC, CRC, BC, ovarian cancer, or pancreatic cancer Cohorts B/B2/BB/BB2 and C/C2/CC/CC2: Subjects with NSCLC, HNSCC, gastroesophageal adenocarinoma, triple negative breast cancer, or urothelial carcinoma whose tumors express PD-L1 according to defined cutoff Cohort D/D2/DD/DD2: Subjects with advanced solid tumor whose tumor(s) express HER2 defined as: =2+ by IHC, Average HER2 copy number =4 signals per cell by in situ hybridization or =4 copies as determined by next generation sequencing Cohort E/E2/EE/EE2: Squamous NSCLC; head and neck cancer that relapsed or progressed following prior cetuximab treatment; CRC subjects who are KRAS/NRAS/BRAF wild-type are required to have progressed/relapsed on prior cetuximab or panitumumab Cohort F/F2/FF/FF2: NSCLC known to have at least one of the following: epidermal growth factor receptor (EGFR) driver mutation(s) and have progressed on or were intolerant to at least one prior line of EGFR Tyrosine Kinase Inhibitor (TKI) or were not candidates for or declined TKI; mesenchymal-epithelial transition (MET) exon 14 skipping mutation that has progressed on or intolerant of at least one prior line of MET TKI or were not candidates for or declined TKI; MET amplification defined as MET/CEP7 ratio =1.8 by Fluorescence in situ hybridization (FISH)
• Has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• For subjects with >1 measurable lesion by RECIST v1.1 that can be safely accessed, willingness to undergo tumor biopsy
• Agrees to contraceptive use for women and men as defined in the protocol

Exclusion Criteria:

• Is a pregnant or breast-feeding female
• Has Eastern Cooperative Oncology Group (ECOG) performance status =2
• Has evidence of insufficient organ function
• Has clinically significant cardiovascular disease including left-ventricular ejection fraction < 45%
• Has received any 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
• Has a known active malignancy in the central nervous system (CNS) that hasn't remained stable for at least 3 months following effective treatment for CNS disease
• Has a non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis or neurodegenerative disease or receipt of medications for these conditions
• Has had any active malignancy other than those studied in this trial within 2 years of the first dose of study therapy
• Is currently receiving or likely to require immunosuppressive therapy
• Has an active bacterial, fungal, or viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
• Has received a live vaccine within 6 weeks prior to start of lympho-conditioning
• Has a known allergy to albumin (human) or dimethyl sulfoxide (DMSO)

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Cancer
• GastroEsophageal Cancer
• Head and Neck Cancer
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer

Intervention

Drug:
• FT536
FT536 is an allogeneic natural killer (NK)-cell immunotherapy
• Cyclophosphamide
Lympho-conditioning agent
• Fludarabine
Lympho-conditioning agent
• IL-2
For Cohort AA ONLY: To be combined with FT536 at the MTD or MAD

Combination Product:
• Avelumab
Monoclonal antibody
• Pembrolizumab
For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab.
• Nivolumab
For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab.
• Atezolizumab
For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab.
• Trastuzumab
Monoclonal antibody
• Cetuximab
Monoclonal antibody
• Amivantamab
Monoclonal antibody

Drug:
• IL-2
For Cohorts BB-FF ONLY: To be combined with FT536 + mAb at the MTD or MAD

Locations

Country	Name	City	State
United States	Hackensack University Medical Center - John Theurer Cancer Center	Hackensack	New Jersey
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	UCLA Division of Hematology-Oncology	Los Angeles	California
United States	NEXT Oncology	San Antonio	Texas
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the Recommended Phase 2 Dose (RP2D)	The RP2Ds of FT536 monotherapy and FT536 + monoclonal antibody (mAbs) will be determined. The RP2D will be determined based on the overall safety and efficacy profile.	Up to approximately 3 years
Primary	Number of Participants with = Adverse Event (AE) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v5.0	The safety and tolerability of FT536 monotherapy and in combination with mAbs will be determined.	Following enrollment completion within dose escalation and expansion, approximately 3 years