Non Small Cell Lung Cancer, Colorectal Cancer, Breast Cancer, Ovarian Cancer, Pancreatic Cancer, Head and Neck Cancer, GastroEsophageal Cancer
Conditions
Brief 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.
Interventions
DRUGFT536
FT536 is an allogeneic natural killer (NK)-cell immunotherapy
DRUGCyclophosphamide
Lympho-conditioning agent
DRUGFludarabine
Lympho-conditioning agent
DRUGIL-2
For Cohort AA ONLY: To be combined with FT536 at the MTD or MAD
COMBINATION_PRODUCTAvelumab
Monoclonal antibody
COMBINATION_PRODUCTPembrolizumab
For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab.
COMBINATION_PRODUCTNivolumab
For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab.
COMBINATION_PRODUCTAtezolizumab
For Cohorts C/CC, the combination product (monoclonal antibody) will be ONE of the following: pembrolizumab, nivolumab, or atezolizumab.
COMBINATION_PRODUCTTrastuzumab
Monoclonal antibody
COMBINATION_PRODUCTCetuximab
Monoclonal antibody
COMBINATION_PRODUCTAmivantamab
Monoclonal antibody
Sponsors
Fate Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Recommended Phase 2 Dose (RP2D) | Up to approximately 3 years | 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. |
| Number of Participants with ≥ Adverse Event (AE) 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 | The safety and tolerability of FT536 monotherapy and in combination with mAbs will be determined. |
Countries
United States
Outcome results
None listed