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

• ClinicalTrials.gov Identifier: NCT03841110
• Recruitment Status: Completed
• First Posted: February 15, 2019
• Last Update Posted: May 1, 2023
• Sponsor: Fate Therapeutics
• Information provided by (Responsible Party): Fate Therapeutics

Tracking Information

• First Submitted Date: February 12, 2019
• First Posted Date: February 15, 2019
• Last Update Posted Date: May 1, 2023
• Actual Study Start Date: February 15, 2019
• Actual Primary Completion Date: November 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 28, 2023)

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).

Original Primary Outcome Measures (submitted: February 12, 2019)

The incidence of subjects with Dose Limiting Toxicities within each dose level cohort. [ Time Frame: Day 29 ]

This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD). The MTD will be the highest dose level cohort with at most one DLT in six subjects.

Current Secondary Outcome Measures (submitted: April 28, 2023)

• 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.
• 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.

Original Secondary Outcome Measures (submitted: February 12, 2019)

• Objective-response rate (ORR) [ Time Frame: Day 29 and every 8 weeks thereafter through Day 366 ]
  Defined as the proportion of subjects who achieve PR or CR at any time on study. Tumor response will be assessed using modified Response Evaluation Criteria In Solid Tumors for immune-based therapeutics (iRECIST) or Response Evaluation Criteria In Lymphomas (RECIL). Only one or the other assessment criterion will be used to measure tumor response. This will depend upon whether solid tumors or lymphomas are being assessed.
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• 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

Study Arms

• Experimental: FT500 Monotherapy
  FT500 administered once weekly for 3 weeks as a monotherapy
  Interventions:

  • Drug: FT500
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
• 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.
  Interventions:

  • Drug: FT500
  • Drug: Nivolumab
  • Drug: Pembrolizumab
  • Drug: Atezolizumab
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
• 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.
  Interventions:

  • Drug: FT500
  • Drug: Nivolumab
  • Drug: Pembrolizumab
  • Drug: Atezolizumab
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Drug: IL-2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 15, 2021): 37
• Original Estimated Enrollment (submitted: February 12, 2019): 64
• Actual Study Completion Date: November 15, 2022
• Actual Primary Completion Date: November 15, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03841110
• Other Study ID Numbers: FT500-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fate Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Fate Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Fate Therapeutics
• Verification Date: April 2023