A Phase I, Open-Label, Multicenter Study of FT536 as Monotherapy and in Combination With Monoclonal Antibodies in Subjects With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Fate Therapeutics
- Enrollment
- 5
- Locations
- 5
- Primary Endpoint
- Determine the Recommended Phase 2 Dose (RP2D)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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)
Arms & Interventions
Cohort A/A2/AA/AA2: FT536 Monotherapy
FT536 monotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), ovarian cancer, or pancreatic cancer.
Intervention: FT536 (Drug)
Cohort A/A2/AA/AA2: FT536 Monotherapy
FT536 monotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), ovarian cancer, or pancreatic cancer.
Intervention: Cyclophosphamide (Drug)
Cohort A/A2/AA/AA2: FT536 Monotherapy
FT536 monotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), ovarian cancer, or pancreatic cancer.
Intervention: Fludarabine (Drug)
Cohort A/A2/AA/AA2: FT536 Monotherapy
FT536 monotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), ovarian cancer, or pancreatic cancer.
Intervention: IL-2 (Drug)
Cohort B/B2/BB/BB2: FT536 + Avelumab
FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: FT536 (Drug)
Cohort B/B2/BB/BB2: FT536 + Avelumab
FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Cyclophosphamide (Drug)
Cohort B/B2/BB/BB2: FT536 + Avelumab
FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Fludarabine (Drug)
Cohort B/B2/BB/BB2: FT536 + Avelumab
FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Avelumab (Combination Product)
Cohort B/B2/BB/BB2: FT536 + Avelumab
FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: IL-2 (Drug)
Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab
FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: FT536 (Drug)
Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab
FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Cyclophosphamide (Drug)
Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab
FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Fludarabine (Drug)
Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab
FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Pembrolizumab (Combination Product)
Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab
FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Nivolumab (Combination Product)
Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab
FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: Atezolizumab (Combination Product)
Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab
FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression.
Intervention: IL-2 (Drug)
Cohort D/D2/DD/DD2: FT536 + Trastuzumab
FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors
Intervention: FT536 (Drug)
Cohort D/D2/DD/DD2: FT536 + Trastuzumab
FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors
Intervention: Cyclophosphamide (Drug)
Cohort D/D2/DD/DD2: FT536 + Trastuzumab
FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors
Intervention: Fludarabine (Drug)
Cohort D/D2/DD/DD2: FT536 + Trastuzumab
FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors
Intervention: Trastuzumab (Combination Product)
Cohort D/D2/DD/DD2: FT536 + Trastuzumab
FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors
Intervention: IL-2 (Drug)
Cohort E/E2/EE/EE2: FT536 + Cetuximab
FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer.
Intervention: Cyclophosphamide (Drug)
Cohort E/E2/EE/EE2: FT536 + Cetuximab
FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer.
Intervention: FT536 (Drug)
Cohort E/E2/EE/EE2: FT536 + Cetuximab
FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer.
Intervention: Fludarabine (Drug)
Cohort E/E2/EE/EE2: FT536 + Cetuximab
FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer.
Intervention: Cetuximab (Combination Product)
Cohort E/E2/EE/EE2: FT536 + Cetuximab
FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer.
Intervention: IL-2 (Drug)
Cohort F/F2/FF/FF2: FT536 + Amivantamab
FT536 + amivantamab in participants with locally advanced or metastatic NSCLC.
Intervention: FT536 (Drug)
Cohort F/F2/FF/FF2: FT536 + Amivantamab
FT536 + amivantamab in participants with locally advanced or metastatic NSCLC.
Intervention: Cyclophosphamide (Drug)
Cohort F/F2/FF/FF2: FT536 + Amivantamab
FT536 + amivantamab in participants with locally advanced or metastatic NSCLC.
Intervention: Fludarabine (Drug)
Cohort F/F2/FF/FF2: FT536 + Amivantamab
FT536 + amivantamab in participants with locally advanced or metastatic NSCLC.
Intervention: Amivantamab (Combination Product)
Cohort F/F2/FF/FF2: FT536 + Amivantamab
FT536 + amivantamab in participants with locally advanced or metastatic NSCLC.
Intervention: IL-2 (Drug)
Outcomes
Primary Outcomes
Determine the Recommended Phase 2 Dose (RP2D)
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
No secondary outcomes reported