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Brief Title: FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors

FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors (Phase 1)

INTRODUCTION

  • Org Study ID: FT500-101
  • Secondary ID: N/A
  • NTC ID: NCT03841110
  • Sponsor: Fate Therapeutics

BRIEF SUMMARY

FT500 is an off-the-shelf, iPSC-derived NK cell product that can bridge innate and adaptive immunity, and has the potential to overcome multiple mechanisms of immune checkpoint inhibitor (ICI) resistance. The preclinical data provide compelling evidence supporting the clinical investigation of FT500 as monotherapy and in combination with ICI in subjects with advanced solid tumors.

  • Overall Status
    Recruiting
  • Start Date
    February 15, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: The incidence of subjects with Dose Limiting Toxicities within each dose level cohort.

Primary Outcome 1 - Timeframe: Day 29

CONDITION

  • Advanced Solid Tumors
  • Lymphoma
  • Gastric Cancer
  • Colorectal Cancer
  • Head and Neck Cancer
  • Squamous Cell Carcinoma
  • EGFR Positive Solid Tumor
  • HER2-positive Breast Cancer
  • Hepatocellular Carcinoma
  • Small Cell Lung Cancer
  • Renal Cell Carcinoma
  • Pancreas Cancer
  • Melanoma
  • NSCLC
  • Urothelial Carcinoma
  • Cervical Cancer
  • Microsatellite Instability
  • Merkel Cell Carcinoma

ELIGIBILITY

Inclusion Criteria:
1. Diagnosis of the following, as per Regimen Cohort:
1A. Regimen A: FT500 Monotherapy (Dose Escalation): An advanced solid tumor malignancy, including lymphoma, in a subject who has failed or refused available FDA-approved therapies and is now a candidate for salvage therapy.
1B. Regimen B and BB (Dose Escalation): FT500 (+ IL-2, Regimen BB only) + ICI: An advanced solid tumor malignancy, including lymphomas, that has progressed on treatment with at least one ICI (ie, nivolumab, pembrolizumab or atezolizumab), in a subject who has also failed or refused other available approved therapies and is now a candidate for salvage therapy.
1C. Regimen B(Dose Expansion): FT500 (+ IL-2, Regimen BB only) + ICI An advanced solid tumor malignancy or lymphoma in a subject with disease relapse or progression on an ICI (nivolumab, pembrolizumab, or atezolizumab) in an approved indication per the respective USPI.
2. Willingness to provide informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICF and in this protoco 3. Age >18 years old at the time of signing the ICF 4. Presence of measurable disease by iRECIST or RECIL criteria, assessed before the start of lympho-conditioning and within 28 days prior to Day 1 5. Contraceptive use by women or men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Female subjects: Women of childbearing potential (WOCBP) must use a highly effective form of contraception from the screening visit until at least 12 months after the final dose of CY, at least 4 months after the final dose of FT500, at least 4 months after the final dose of pembrolizumab, and at least 5 months after the final dose of nivolumab or atezolizumab, whichever is latest.
Male subjects: Males must be sterile (biologically or surgically) or use a highly effective method of contraception from the screening visit until at least 14 months after the final dose of CY, at least 6 months after the final dose of FT500, at least 6 months after the final dose of pembrolizumab, and at least 7 months after the final dose of nivolumab or atezolizumab, whichever is latest 6. Willingness to comply with study procedures through the planned study duration. For patients with >1 measurable lesion, agreement to undergo a biopsy from a safely accessible site per Investigator assessment for exploratory biomarker assessments.
7. Provision of signed and dated ICF to agree to participate, at time of withdrawal or completion of this study, in Fate Therapeutics' long-term, non-interventional, observational study, FT-003
Exclusion Criteria:
All Subjects:
Females who are pregnant or breastfeeding

- ECOG performance status ≥ 2.
Evidence of insufficient organ function as determined by any one of the following:
Neutrophils <1000/µL or platelets <75,000/µL. - Estimated creatinine clearance <50 mL/minute (Cockcroft-gault). - Total bilirubin >2 x upper limit normal (ULN) with the exception of subjects with Gilbert's Syndrome or known liver metastases.

- Aspartate aminotransferase (AST) >3 x ULN, or alanine aminotransferase (ALT) >3 x ULN. For subjects with known liver metastases, AST or ALT >5 x ULN.

- Oxygen saturation <90% on room air - Left ventricular ejection fraction (LVEF) <40% (eg by echocardiogram (ECHO) or ] multi-gated acquisition (MUGA) scan). - Receipt of any biological therapy, chemotherapy, or radiation (except palliative radiation) within 2 weeks prior to Day 1. Subjects in Regimen B currently taking an ICI must interrupt ICI dosing at least 2 weeks prior to Day 1. - CNS metastases that have not been treated; or treated CNS metastases that have not been stable for at least 4 weeks. - Clinically significant cardiovascular disease, including stroke or myocardial infarction within 6 months prior to first study medication; or the presence of unstable angina or congestive heart failure of New York Heart Association grade 2 or higher. - Currently receiving or likely to require systemic immunosuppressive therapy (eg, prednisone >5 mg daily) for any reason from Day -7 to Day 29.

- Uncontrolled infections.

- Known allergy to the following FT500 components: Albumin (Human) or DMSO.

- Presence of any medical or social issues that are likely to interfere with study conduct, or may cause increased risk to subject.

- Any medical condition or clinical laboratory abnormality that, per Investigator or Medical Monitor judgement, precludes safe participation in and completion of the study, or that could affect compliance with protocol conduct or interpretation of results Subjects who have had prior receipt of a Fate Therapeutics investigational human iPSC product may be eligible for the study with approval from the Medical Monitor.
Additional Exclusion Criteria for Regimen B: FT500 + ICI:
11. Subjects who experienced an ICI-related adverse reaction that resulted in discontinuation of the ICI.
12. Presence or history of autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma, Crohn's disease, ulcerative colitis), except for subjects with isolated vitiligo, atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and controlled thyroid disease.
13. Subjects who have received an allograft organ transplant.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Jeff Chou, MD

Role: Study Director

Affiliation: Fate Therapeutics

Overall Contact

Name: Jeff Chou, MD

Phone: 858-875-1800, 858-875-1800

Email: clinical@fatetherapeutics.com

LOCATION

Facility Status Contact
Facility: UCSD Moores Cancer Center
San Diego, California 92093
United States
Status: Recruiting Contact: N/A
Facility: University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota 55455
United States
Status: Recruiting Contact: N/A
Facility: Hackensack University Medical Center/John Theurer Cancer Center
Hackensack, New Jersey 07601
United States
Status: Recruiting Contact: N/A
Facility: MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A