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

NCT ID: NCT03841110

Last Updated: 2023-05-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-15

Study Completion Date

2022-11-15

Brief Summary

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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.

Detailed Description

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Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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FT500 Monotherapy

FT500 administered once weekly for 3 weeks as a monotherapy

Group Type EXPERIMENTAL

FT500

Intervention Type DRUG

FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy

Cyclophosphamide

Intervention Type DRUG

Lympho-conditioning agent

Fludarabine

Intervention Type DRUG

Lympho-conditioning agent

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.

Group Type EXPERIMENTAL

FT500

Intervention Type DRUG

FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy

Nivolumab

Intervention Type DRUG

Immune Checkpoint Inhibitor

Pembrolizumab

Intervention Type DRUG

Immune Checkpoint Inhibitor

Atezolizumab

Intervention Type DRUG

Immune Checkpoint Inhibitor

Cyclophosphamide

Intervention Type DRUG

Lympho-conditioning agent

Fludarabine

Intervention Type DRUG

Lympho-conditioning agent

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.

Group Type EXPERIMENTAL

FT500

Intervention Type DRUG

FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy

Nivolumab

Intervention Type DRUG

Immune Checkpoint Inhibitor

Pembrolizumab

Intervention Type DRUG

Immune Checkpoint Inhibitor

Atezolizumab

Intervention Type DRUG

Immune Checkpoint Inhibitor

Cyclophosphamide

Intervention Type DRUG

Lympho-conditioning agent

Fludarabine

Intervention Type DRUG

Lympho-conditioning agent

IL-2

Intervention Type DRUG

Biologic response modifier

Interventions

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FT500

FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy

Intervention Type DRUG

Nivolumab

Immune Checkpoint Inhibitor

Intervention Type DRUG

Pembrolizumab

Immune Checkpoint Inhibitor

Intervention Type DRUG

Atezolizumab

Immune Checkpoint Inhibitor

Intervention Type DRUG

Cyclophosphamide

Lympho-conditioning agent

Intervention Type DRUG

Fludarabine

Lympho-conditioning agent

Intervention Type DRUG

IL-2

Biologic response modifier

Intervention Type DRUG

Other Intervention Names

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OPDIVO KEYTRUDA TECENTRIQ Proleukin Aldesleukin

Eligibility Criteria

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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.


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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fate Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fate Trial Disclosure

Role: STUDY_DIRECTOR

[email protected]

Locations

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UCSD Moores Cancer Center

San Diego, California, United States

Site Status

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Hackensack University Medical Center/John Theurer Cancer Center

Hackensack, New Jersey, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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FT500-101

Identifier Type: -

Identifier Source: org_study_id

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