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

April 28, 2023 updated by: Fate Therapeutics

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

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 participants with advanced solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92093
        • UCSD Moores Cancer Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Masonic Cancer Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center/John Theurer Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 participant 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 participant 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 participant 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 protocol.

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.

5a. Female participants: 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.

5b. Male participants: 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 participants:

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: 3a. Neutrophils <1000/µL or platelets <75,000/µL. 3b. Estimated creatinine clearance <50 mL/minute (Cockcroft-gault). 3c. Total bilirubin >2 x upper limit normal (ULN) with the exception of participants with Gilbert's Syndrome or known liver metastases.

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

3e. Oxygen saturation <90% on room air. 3f. 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. Participants 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 participant.

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. Participants 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. Participants 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 participants with isolated vitiligo, atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and controlled thyroid disease.

13. Participants who have received an allograft organ transplant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FT500 Monotherapy
FT500 administered once weekly for 3 weeks as a monotherapy
Drug: Cyclophosphamide
Lympho-conditioning agent
Drug: Fludarabine
Lympho-conditioning agent
Drug: FT500
FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy
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: Cyclophosphamide
Lympho-conditioning agent
Drug: Fludarabine
Lympho-conditioning agent
Drug: FT500
FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy
Drug: Nivolumab
Immune Checkpoint Inhibitor
Other Names:
  • OPDIVO
Drug: Pembrolizumab
Immune Checkpoint Inhibitor
Other Names:
  • KEYTRUDA
Drug: Atezolizumab
Immune Checkpoint Inhibitor
Other Names:
  • TECENTRIQ
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: IL-2
Biologic response modifier
Other Names:
  • Proleukin
  • Aldesleukin
Drug: Cyclophosphamide
Lympho-conditioning agent
Drug: Fludarabine
Lympho-conditioning agent
Drug: FT500
FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy
Drug: Nivolumab
Immune Checkpoint Inhibitor
Other Names:
  • OPDIVO
Drug: Pembrolizumab
Immune Checkpoint Inhibitor
Other Names:
  • KEYTRUDA
Drug: Atezolizumab
Immune Checkpoint Inhibitor
Other Names:
  • TECENTRIQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of participants with Dose Limiting Toxicities (DLTs) within each dose level cohort.
Time Frame: Day 29
The incidence of participants with DLTs within each assessed dose level cohort to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD).
Day 29

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective-response rate (ORR)
Time Frame: Day 29 and every 8 weeks thereafter through Day 366
ORR is defined as the proportion of participants who achieve immune partial reponse/partial response (iPR/PR) or immune complete response/complete response (iCR/CR). Tumor response will be assessed using modified Response Evaluation Criteria in Solid Tumors (iRECIST) or Response Evaluation Criteria in Lymphoma (RECIL), as applicable.
Day 29 and every 8 weeks thereafter through Day 366
Duration of FT500 persistence
Time Frame: Day 1 through Day 366
Duration of FT500 response is defined as duration from Day 1 to undetectable levels of FT500 cells per uL blood.
Day 1 through Day 366

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fate Therapeutics

Investigators

  • Study Director: Fate Trial Disclosure, FateTrialDisclosure@fatetherapeutics.com

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2019

Primary Completion (Actual)

November 15, 2022

Study Completion (Actual)

November 15, 2022

Study Registration Dates

First Submitted

February 12, 2019

First Submitted That Met QC Criteria

February 12, 2019

First Posted (Actual)

February 15, 2019

Study Record Updates

Last Update Posted (Actual)

May 1, 2023

Last Update Submitted That Met QC Criteria

April 28, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FT500-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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