FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors
Study Details
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 subjects with advanced solid tumors.
Study Design
Arms and Interventions
| 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 Names:
Drug: Pembrolizumab
Immune Checkpoint Inhibitor
Other Names:
Drug: Atezolizumab
Immune Checkpoint Inhibitor
Other Names:
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 Names:
Drug: Pembrolizumab
Immune Checkpoint Inhibitor
Other Names:
Drug: Atezolizumab
Immune Checkpoint Inhibitor
Other Names:
Drug: Cyclophosphamide
Lympho-conditioning agent
Drug: Fludarabine
Lympho-conditioning agent
Drug: IL-2
Biologic response modifier
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The incidence of subjects with Dose Limiting Toxicities within each dose level cohort. [Day 29]
The incidence of subjects with DLTs within each assessed dose level cohort to determine the MTD or MAD.
Secondary Outcome Measures
- Objective-response rate (ORR) [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.
- Duration of FT500 persistence [Day 1 through Day 366]
defined as duration from Day 1 to undetectable levels of FT500 cells per uL blood.
Eligibility Criteria
Criteria
Inclusion Criteria:
- 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.
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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
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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.
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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.
-
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
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ECOG performance status ≥ 2.
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Evidence of insufficient organ function as determined by any one of the following:
-
Neutrophils <1000/µL or platelets <75,000/µL.
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Estimated creatinine clearance <50 mL/minute (Cockcroft-gault).
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Total bilirubin >2 x upper limit normal (ULN) with the exception of subjects with Gilbert's Syndrome or known liver metastases.
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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.
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Oxygen saturation <90% on room air
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Left ventricular ejection fraction (LVEF) <40% (eg by echocardiogram (ECHO) or ] multi-gated acquisition (MUGA) scan).
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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.
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CNS metastases that have not been treated; or treated CNS metastases that have not been stable for at least 4 weeks.
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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.
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Currently receiving or likely to require systemic immunosuppressive therapy (eg, prednisone >5 mg daily) for any reason from Day -7 to Day 29.
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Uncontrolled infections.
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Known allergy to the following FT500 components: Albumin (Human) or DMSO.
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Presence of any medical or social issues that are likely to interfere with study conduct, or may cause increased risk to subject.
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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:
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Subjects who experienced an ICI-related adverse reaction that resulted in discontinuation of the ICI.
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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.
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Subjects who have received an allograft organ transplant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCSD Moores Cancer Center | San Diego | California | United States | 92093 |
| 2 | University of Minnesota Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
| 3 | Hackensack University Medical Center/John Theurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
| 4 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Fate Therapeutics
Investigators
- Study Director: Jeff Chou, MD, Fate Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FT500-101