FT536 Monotherapy and in Combination With Monoclonal Antibodies in Advanced Solid Tumors
- Conditions
- Head and Neck CancerOvarian CancerPancreatic CancerNon Small Cell Lung CancerColorectal CancerGastroEsophageal CancerBreast Cancer
- Interventions
- Combination Product: AvelumabCombination Product: PembrolizumabCombination Product: TrastuzumabCombination Product: CetuximabCombination Product: AmivantamabCombination Product: NivolumabCombination Product: Atezolizumab
- Registration Number
- NCT05395052
- Lead Sponsor
- Fate Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort B/B2/BB/BB2: FT536 + Avelumab Fludarabine FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort B/B2/BB/BB2: FT536 + Avelumab Avelumab FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort A/A2/AA/AA2: FT536 Monotherapy FT536 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. Cohort A/A2/AA/AA2: FT536 Monotherapy Cyclophosphamide 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. Cohort A/A2/AA/AA2: FT536 Monotherapy Fludarabine 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. Cohort A/A2/AA/AA2: FT536 Monotherapy IL-2 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. Cohort B/B2/BB/BB2: FT536 + Avelumab FT536 FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort B/B2/BB/BB2: FT536 + Avelumab Cyclophosphamide FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab Fludarabine FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort B/B2/BB/BB2: FT536 + Avelumab IL-2 FT536 + avelumab combination therapy in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab FT536 FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab Cyclophosphamide FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab Pembrolizumab FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab Nivolumab FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort E/E2/EE/EE2: FT536 + Cetuximab Fludarabine FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer. Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab Atezolizumab FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort C/C2/CC/CC2: FT536 + Pembrolizumab, Nivolumab, or Atezolizumab IL-2 FT536 + pembrolizumab, nivolumab, or atezolizumab in participants with locally advanced or metastatic solid tumor indications with documented PD-L1 expression. Cohort D/D2/DD/DD2: FT536 + Trastuzumab FT536 FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors Cohort D/D2/DD/DD2: FT536 + Trastuzumab Cyclophosphamide FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors Cohort D/D2/DD/DD2: FT536 + Trastuzumab Fludarabine FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors Cohort D/D2/DD/DD2: FT536 + Trastuzumab Trastuzumab FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors Cohort E/E2/EE/EE2: FT536 + Cetuximab FT536 FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer. Cohort E/E2/EE/EE2: FT536 + Cetuximab Cyclophosphamide FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer. Cohort E/E2/EE/EE2: FT536 + Cetuximab Cetuximab FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer. Cohort E/E2/EE/EE2: FT536 + Cetuximab IL-2 FT536 + cetuximab in participants with locally advanced or metastatic squamous NSCLC, CRC, or head and neck cancer. Cohort F/F2/FF/FF2: FT536 + Amivantamab FT536 FT536 + amivantamab in participants with locally advanced or metastatic NSCLC. Cohort F/F2/FF/FF2: FT536 + Amivantamab Fludarabine FT536 + amivantamab in participants with locally advanced or metastatic NSCLC. Cohort F/F2/FF/FF2: FT536 + Amivantamab Amivantamab FT536 + amivantamab in participants with locally advanced or metastatic NSCLC. Cohort F/F2/FF/FF2: FT536 + Amivantamab IL-2 FT536 + amivantamab in participants with locally advanced or metastatic NSCLC. Cohort D/D2/DD/DD2: FT536 + Trastuzumab IL-2 FT536 + trastuzumab in participants with locally advanced or metastatic documented human epidermal growth factor receptor 2 (HER2+) expressing tumors Cohort F/F2/FF/FF2: FT536 + Amivantamab Cyclophosphamide FT536 + amivantamab in participants with locally advanced or metastatic NSCLC.
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (5)
Hackensack University Medical Center - John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
UCLA Division of Hematology-Oncology
🇺🇸Los Angeles, California, United States
Carolina BioOncology Institute
🇺🇸Huntersville, North Carolina, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States