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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03841110
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : October 25, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
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 Drug: FT500 Drug: Nivolumab Drug: Pembrolizumab Drug: Atezolizumab Drug: Cyclophosphamide Drug: Fludarabine Drug: IL-2 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors (Phase 1)
Actual Study Start Date : February 15, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Experimental: FT500 Monotherapy
FT500 administered once weekly for 3 weeks as a monotherapy
Drug: FT500
FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy

Drug: Cyclophosphamide
Lympho-conditioning agent

Drug: Fludarabine
Lympho-conditioning agent

Experimental: FT500 in Combination with Immune Checkpoint Inhibitor
FT500 administered once weekly for 3 weeks in combination with one of the following immune checkpoint inhibitors: nivolumab, pembrolizumab or atezolizumab.
Drug: FT500
FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy

Drug: Nivolumab
Immune Checkpoint Inhibitor
Other Name: OPDIVO

Drug: Pembrolizumab
Immune Checkpoint Inhibitor
Other Name: KEYTRUDA

Drug: Atezolizumab
Immune Checkpoint Inhibitor
Other Name: TECENTRIQ

Drug: Cyclophosphamide
Lympho-conditioning agent

Drug: Fludarabine
Lympho-conditioning agent

Experimental: FT500 +IL-2 in Combination with Immune Checkpoint Inhibitor
FT500 + IL-2 administered once weekly for 3 weeks in combination with one of the following immune checkpoint inhibitors: nivolumab, pembrolizumab or atezolizumab.
Drug: FT500
FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy

Drug: Nivolumab
Immune Checkpoint Inhibitor
Other Name: OPDIVO

Drug: Pembrolizumab
Immune Checkpoint Inhibitor
Other Name: KEYTRUDA

Drug: Atezolizumab
Immune Checkpoint Inhibitor
Other Name: TECENTRIQ

Drug: Cyclophosphamide
Lympho-conditioning agent

Drug: Fludarabine
Lympho-conditioning agent

Drug: IL-2
Biologic response modifier
Other Names:
  • Proleukin
  • Aldesleukin




Primary Outcome Measures :
  1. The incidence of subjects with Dose Limiting Toxicities within each dose level cohort. [ Time Frame: Day 29 ]
    The incidence of subjects with DLTs within each assessed dose level cohort to determine the MTD or MAD.


Secondary Outcome Measures :
  1. Objective-response rate (ORR) [ Time Frame: Day 29 and every 8 weeks thereafter through Day 366 ]

    defined as the proportion of subjects who achieve iPR/PR or iCR/CR. Tumor response will be assessed using iRECIST or RECIL, as applicable.

    Protocol FT500-101 FT500 Monotherapy and in Combination with Immune Checkpoint Inhibitors Page 16 of 121 Protocol Version 5.0 Fate Therapeutics, Inc.⎯Confidential and Proprietary The "i" prefix will be used throughout this protocol to denote iRECIST responses of iCR, iPR, iSD, iUPD, and iCPD.


  2. Duration of FT500 persistence [ Time Frame: Day 1 through Day 366 ]
    defined as duration from Day 1 to undetectable levels of FT500 cells per uL blood.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  1. 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.
  2. 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:

  1. Females who are pregnant or breastfeeding
  2. ECOG performance status ≥ 2.
  3. Evidence of insufficient organ function as determined by any one of the following:

    1. Neutrophils <1000/µL or platelets <75,000/µL.
    2. Estimated creatinine clearance <50 mL/minute (Cockcroft-gault).
    3. Total bilirubin >2 x upper limit normal (ULN) with the exception of subjects with Gilbert's Syndrome or known liver metastases.
    4. 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.
    5. Oxygen saturation <90% on room air
    6. Left ventricular ejection fraction (LVEF) <40% (eg by echocardiogram (ECHO) or ] multi-gated acquisition (MUGA) scan).
  4. 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.
  5. CNS metastases that have not been treated; or treated CNS metastases that have not been stable for at least 4 weeks.
  6. 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.
  7. Currently receiving or likely to require systemic immunosuppressive therapy (eg, prednisone >5 mg daily) for any reason from Day -7 to Day 29.
  8. Uncontrolled infections.
  9. Known allergy to the following FT500 components: Albumin (Human) or DMSO.
  10. Presence of any medical or social issues that are likely to interfere with study conduct, or may cause increased risk to subject.
  11. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03841110


Contacts
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Contact: Kimberly Musni 858-875-1800 clinical@fatetherapeutics.com
Contact: Karen Albers 858-875-1800

Locations
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United States, California
UCSD Moores Cancer Center Recruiting
San Diego, California, United States, 92093
United States, Minnesota
University of Minnesota Masonic Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
United States, New Jersey
Hackensack University Medical Center/John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Fate Therapeutics
Investigators
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Study Director: Jeff Chou, MD Fate Therapeutics
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Responsible Party: Fate Therapeutics
ClinicalTrials.gov Identifier: NCT03841110    
Other Study ID Numbers: FT500-101
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: October 25, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fate Therapeutics:
Advanced Solid Tumor
Lymphoma
Breast Cancer
Head and Neck Cancer
Head and Neck
Squamous Cell Carcinoma
Gastric Cancer
Colorectal Cancer
Immunotherapy
NK cell therapy
Melanoma
Checkpoint Inhibitor
Immune Checkpoint Inhibitor
Monoclonal Antibody
Cell therapy
Cellular therapy
nivolumab
pembrolizumab
atezolizumab
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma
Neoplasms
Colorectal Neoplasms
Melanoma
Carcinoma, Squamous Cell
Stomach Neoplasms
Head and Neck Neoplasms
Small Cell Lung Carcinoma
Pancreatic Neoplasms
Microsatellite Instability
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms by Site
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Adenocarcinoma
Stomach Diseases