search
Back to results

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

Primary Purpose

Advanced Solid Tumors, Lymphoma, Gastric Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
FT500
Nivolumab
Pembrolizumab
Atezolizumab
Cyclophosphamide
Fludarabine
IL-2
Sponsored by
Fate Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumors focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCSD Moores Cancer Center
  • University of Minnesota Masonic Cancer Center
  • Hackensack University Medical Center/John Theurer Cancer Center
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

FT500 Monotherapy

FT500 in Combination with Immune Checkpoint Inhibitor

FT500 +IL-2 in Combination with Immune Checkpoint Inhibitor

Arm Description

FT500 administered once weekly for 3 weeks as a monotherapy

FT500 administered once weekly for 3 weeks in combination with one of the following immune checkpoint inhibitors: nivolumab, pembrolizumab or atezolizumab.

FT500 + IL-2 administered once weekly for 3 weeks in combination with one of the following immune checkpoint inhibitors: nivolumab, pembrolizumab or atezolizumab.

Outcomes

Primary Outcome Measures

The incidence of participants with Dose Limiting Toxicities (DLTs) within each dose level cohort.
The incidence of participants with DLTs within each assessed dose level cohort to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD).

Secondary Outcome Measures

Objective-response rate (ORR)
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.
Duration of FT500 persistence
Duration of FT500 response is defined as duration from Day 1 to undetectable levels of FT500 cells per uL blood.

Full Information

First Posted
February 12, 2019
Last Updated
April 28, 2023
Sponsor
Fate Therapeutics
search

1. Study Identification

Unique Protocol Identification Number
NCT03841110
Brief Title
FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors
Official Title
FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors (Phase 1)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
February 15, 2019 (Actual)
Primary Completion Date
November 15, 2022 (Actual)
Study Completion Date
November 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fate Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 participants with advanced solid tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FT500 Monotherapy
Arm Type
Experimental
Arm Description
FT500 administered once weekly for 3 weeks as a monotherapy
Arm Title
FT500 in Combination with Immune Checkpoint Inhibitor
Arm Type
Experimental
Arm Description
FT500 administered once weekly for 3 weeks in combination with one of the following immune checkpoint inhibitors: nivolumab, pembrolizumab or atezolizumab.
Arm Title
FT500 +IL-2 in Combination with Immune Checkpoint Inhibitor
Arm Type
Experimental
Arm Description
FT500 + IL-2 administered once weekly for 3 weeks in combination with one of the following immune checkpoint inhibitors: nivolumab, pembrolizumab or atezolizumab.
Intervention Type
Drug
Intervention Name(s)
FT500
Intervention Description
FT500 is an allogeneic, iPSC-derived Natural Killer (NK) cell cancer immunotherapy
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
OPDIVO
Intervention Description
Immune Checkpoint Inhibitor
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
KEYTRUDA
Intervention Description
Immune Checkpoint Inhibitor
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
TECENTRIQ
Intervention Description
Immune Checkpoint Inhibitor
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Lympho-conditioning agent
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Lympho-conditioning agent
Intervention Type
Drug
Intervention Name(s)
IL-2
Other Intervention Name(s)
Proleukin, Aldesleukin
Intervention Description
Biologic response modifier
Primary Outcome Measure Information:
Title
The incidence of participants with Dose Limiting Toxicities (DLTs) within each dose level cohort.
Description
The incidence of participants with DLTs within each assessed dose level cohort to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD).
Time Frame
Day 29
Secondary Outcome Measure Information:
Title
Objective-response rate (ORR)
Description
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.
Time Frame
Day 29 and every 8 weeks thereafter through Day 366
Title
Duration of FT500 persistence
Description
Duration of FT500 response is defined as duration from Day 1 to undetectable levels of FT500 cells per uL blood.
Time Frame
Day 1 through Day 366

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fate Trial Disclosure
Organizational Affiliation
FateTrialDisclosure@fatetherapeutics.com
Official's Role
Study Director
Facility Information:
Facility Name
UCSD Moores Cancer Center
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of Minnesota Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Hackensack University Medical Center/John Theurer Cancer Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs