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

Sponsor

Fate Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05395052

Collaborator

(none)

322

Enrollment

Location

Arms

Anticipated Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1 dose-finding study of FT536 monotherapy and in combination with monoclonal antibodies.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Colorectal Cancer Breast Cancer Ovarian Cancer Pancreatic Cancer Head and Neck Cancer GastroEsophageal Cancer	Drug: FT536 Drug: Cyclophosphamide Drug: Fludarabine Drug: IL-2 Combination Product: Avelumab Combination Product: Pembrolizumab Combination Product: Nivolumab Combination Product: Atezolizumab Combination Product: Trastuzumab Combination Product: Cetuximab Combination Product: Amivantamab Drug: IL-2	Phase 1

Detailed Description

This is a Phase 1 dose-finding study of FT536 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

322 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 31, 2022

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Apr 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A/AA FT536 monotherapy in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), ovarian cancer, or pancreatic cancer	Drug: FT536 FT536 is an allogeneic natural killer (NK)-cell immunotherapy Other Names: NK Cell Therapy Drug: Cyclophosphamide Lympho-conditioning agent Other Names: Cy Drug: Fludarabine Lympho-conditioning agent Other Names: Flu Drug: IL-2 For Cohort AA ONLY: To be combined with FT536 at the MTD or MAD Other Names: Interleukin-2
Experimental: Cohort B/BB FT536 plus anti-programmed cell death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibodies in subjects with locally advanced or metastatic solid tumor indications with documented PD-L1 expression	Drug: FT536 FT536 is an allogeneic natural killer (NK)-cell immunotherapy Other Names: NK Cell Therapy Drug: Cyclophosphamide Lympho-conditioning agent Other Names: Cy Drug: Fludarabine Lympho-conditioning agent Other Names: Flu Combination Product: Avelumab Monoclonal antibody Other Names: Bavencio Drug: IL-2 For Cohorts BB-FF ONLY: To be combined with FT536 + mAb at the MTD or MAD Other Names: Interleukin-2
Experimental: Cohort C/CC FT536 plus anti-PD-1/PD-L1 antibodies in subjects with locally advanced or metastatic solid tumor indications with documented PD-L1 expression	Drug: FT536 FT536 is an allogeneic natural killer (NK)-cell immunotherapy Other Names: NK Cell Therapy Drug: Cyclophosphamide Lympho-conditioning agent Other Names: Cy Drug: Fludarabine Lympho-conditioning agent Other Names: Flu Combination Product: Pembrolizumab For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab. Other Names: Keytruda Combination Product: Nivolumab For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab. Other Names: Opdivo Combination Product: Atezolizumab For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab. Other Names: Tecentriq Drug: IL-2 For Cohorts BB-FF ONLY: To be combined with FT536 + mAb at the MTD or MAD Other Names: Interleukin-2
Experimental: Cohort D/DD FT536 plus trastuzumab in subjects with advanced documented human epidermal growth factor receptor 2 (HER2+) expressing tumors	Drug: FT536 FT536 is an allogeneic natural killer (NK)-cell immunotherapy Other Names: NK Cell Therapy Drug: Cyclophosphamide Lympho-conditioning agent Other Names: Cy Drug: Fludarabine Lympho-conditioning agent Other Names: Flu Combination Product: Trastuzumab Monoclonal antibody Other Names: Herceptin Drug: IL-2 For Cohorts BB-FF ONLY: To be combined with FT536 + mAb at the MTD or MAD Other Names: Interleukin-2
Experimental: Cohort E/EE FT536 plus cetuximab in subjects with locally advanced or metastatic squamous NSCLC, head and neck cancer, or CRC	Drug: FT536 FT536 is an allogeneic natural killer (NK)-cell immunotherapy Other Names: NK Cell Therapy Drug: Cyclophosphamide Lympho-conditioning agent Other Names: Cy Drug: Fludarabine Lympho-conditioning agent Other Names: Flu Combination Product: Cetuximab Monoclonal antibody Other Names: Erbitux Drug: IL-2 For Cohorts BB-FF ONLY: To be combined with FT536 + mAb at the MTD or MAD Other Names: Interleukin-2
Experimental: Cohort F/FF FT536 plus amivantamab in subjects with locally advanced or metastatic NSCLC	Drug: FT536 FT536 is an allogeneic natural killer (NK)-cell immunotherapy Other Names: NK Cell Therapy Drug: Cyclophosphamide Lympho-conditioning agent Other Names: Cy Drug: Fludarabine Lympho-conditioning agent Other Names: Flu Combination Product: Amivantamab Monoclonal antibody Other Names: Rybrevant Drug: IL-2 For Cohorts BB-FF ONLY: To be combined with FT536 + mAb at the MTD or MAD Other Names: Interleukin-2

Outcome Measures

Primary Outcome Measures

Define recommended phase 2 dose (RP2D) [Following dose escalation and dose expansion within each cohort, approximately 3 years]
To define the RP2D of FT536 monotherapy and in combination with monoclonal antibody (mAbs)
Incidence, nature, and severity of adverse events (AEs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v5.0 [Following enrollment completion within dose escalation and expansion, approximately 3 years]
To evaluate the safety and tolerability of FT536 monotherapy and in combination with mAbs

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects 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/AA: NSCLC, CRC, BC, ovarian cancer, or pancreatic cancer

Cohorts B/BB and C/CC: Subjects with NSCLC, HNSCC, gastroesophageal adenocarinoma, triple negative breast cancer, or urothelial carcinoma whose tumors express PD-L1 according to defined cutoff

Cohort D/DD: 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/EE: Squamous NSCLC; head and neck cancer that relapsed or progressed following prior cetuximab treatment; CRC subjects who are KRAS/NRAS wild-type are required to have progressed/relapsed on prior cetuximab or panitumumab

Cohort F/FF: 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)

Aged 18 years old or greater
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
Contraceptive use for women and men as defined in the protocol

Exclusion Criteria:

Pregnant or breast-feeding women
Eastern Cooperative Oncology Group (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't 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 hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
Live vaccine within 6 weeks prior to start of lympho-conditioning
Known allergy to albumin (human) or dimethyl sulfoxide (DMSO)