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

• ClinicalTrials.gov Identifier: NCT03841110
• Recruitment Status: Recruiting
• First Posted: February 15, 2019
• Last Update Posted: October 25, 2021
• Sponsor: Fate Therapeutics
• Information provided by (Responsible Party): Fate Therapeutics

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.

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

Study Design

• 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

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 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

Outcome Measures

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.

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

Contact: Kimberly Musni; 858-875-1800; clinical@fatetherapeutics.com

Contact: Karen Albers; 858-875-1800

Locations

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

• Study Director: Jeff Chou, MD; Fate Therapeutics

More Information

• Responsible Party: Fate Therapeutics
• ClinicalTrials.gov Identifier: NCT03841110
• Other Study ID Numbers: FT500-101
• First Posted: February 15, 2019
• Last Update Posted: October 25, 2021
• Last Verified: October 2021

• 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:

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