FT538 in Subjects With Advanced Hematologic Malignancies

A Phase I, Open-Label, Multicenter Study of FT538 as Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination With Monoclonal Antibodies in Relapsed/Refractory Multiple Myeloma

This is a Phase I dose-finding study of FT538 as monotherapy in acute myeloid leukemia (AML) and in combination with monoclonal antibodies in multiple myeloma (MM). The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Multiple Myeloma; Myeloma; AML, Adult
• Intervention / Treatment: Drug: Fludarabine; Drug: FT538; Drug: Cyclophosphamide; Drug: Daratumumab; Drug: Elotuzumab

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mohamed Elgendy; Phone Number: 8588751800; Email: clinical@fatetherapeutics.com
• Study Contact Backup: Name: Dennis Hazekamp; Phone Number: 8588751800; Email: clinical@fatetherapeutics.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute at Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78704
      • St. David's South Austin Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of one of the following by treatment regimen:

   • Regimen A (FT538 monotherapy in r/r AML)

     • Primary refractory AML, or
     • Relapsed AML, defined as not in CR after one or more re-induction attempts; if >60 years of age, prior re-induction therapy is not required

   • Regimens B or C (FT538 + mAb in r/r MM)

     • Regimen B only: MM that has relapsed or progressed after at least two lines of therapies, including a proteasome inhibitor and an immunomodulatory drug
     • Regimen C only: MM that has relapsed or progressed after proteasome inhibitor therapy, and immunomodulatory therapy
     • Regimen B and Regimen C: Measurable disease as defined in the protocol
2. Capable of giving signed informed consent
3. Agreement to comply with study procedures as described in the Schedule of Activities
4. Agrees to contraceptive use as described in the protocol

Exclusion Criteria:

1. Females who are pregnant or breastfeeding
2. ECOG Performance Status ≥ 2
3. Evidence of insufficient hematologic function as defined in the protocol
4. Evidence of insufficient organ function defined as defined by the protocol
5. Clinically significant cardiovascular disease as defined by the protocol
6. Known active central nervous system (CNS) involvement by malignancy
7. Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
8. Currently receiving or likely to require systemic immunosuppressive therapy for any reason during the treatment period
9. Clinically significant infections including HIV, HBV and HCV
10. Live vaccine <6 weeks prior to start of lympho-conditioning
11. Receipt of an allograft organ transplant
12. Prior allogeneic HSCT or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host therapy
13. Known allergy to albumin (human) or DMSO
14. Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject

15. Any medical condition or clinical laboratory abnormality that per investigator or Medical Monitor judgement precludes safe participation in and completion of the study, or which could affect compliance with protocol conduct or interpretation of results

    Exclusion Criteria Specific to Regimen A (r/r AML)

16. Diagnosis of promyelocytic leukemia with t(15;17) translocation

17. Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Day 1

    Exclusion Criteria Specific to Regimens B and C (r/r MM)

18. Plasma cell leukemia defined as a plasma cell count >2000/mm3
19. Leptomeningeal involvement of MM
20. Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to the first dose of mAb
21. Allergy or hypersensitivity to antibodies or antibody-related proteins

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FT538 Monotherapy; FT538 monotherapy in subjects with r/r AML	Drug: Fludarabine; Lympho-conditioning Agent; Drug: FT538; Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell; Drug: Cyclophosphamide; Lympho-conditioning Agent
Experimental: FT538 in Combination with Daratumumab; FT538 in combination with daratumumab in subjects with r/r MM	Drug: Fludarabine; Lympho-conditioning Agent; Drug: FT538; Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell; Drug: Cyclophosphamide; Lympho-conditioning Agent; Drug: Daratumumab; Monoclonal Antibody, CD38, Anti-CD38; Other Names: Darzalex
Experimental: FT538 in Combination with Elotuzumab; FT538 in combination with elotuzumab in subjects with r/r MM	Drug: Fludarabine; Lympho-conditioning Agent; Drug: FT538; Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell; Drug: Cyclophosphamide; Lympho-conditioning Agent; Drug: Elotuzumab; Monoclonal Antibody; Other Names: Empliciti

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose-limiting toxicities (DLTs) within each dose level cohort	Cycle 1, Up to Day 29
Nature of dose-limiting toxicities within each dose level cohort	Cycle 1, Up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, nature, and severity of adverse events (AEs) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r multiple myeloma		Up to 5 years
Objective response rate (ORR) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM	Proportion of subjects who achieve a CR, CRMRD-, CRi, MLFS, or PR, as determined by the investigator according to 2017 ELN criteria for AML, and the proportion of subjects with a best overall response of sCR, CR, VGPR, or PR, as determined by the investigator according to standard IMWG for MM response criteria	From baseline tumor assessment up to approximately 2 years after last dose of FT538
Duration of response (DOR) of FT538 in combination with daratumumab or elotuzumab in r/r MM	Defined as the duration from the first occurrence of a documented objective response until the time of disease progression or relapse, or death due to progressive disease, as determined by the investigator according to standard IMWG response criteria	Up to 15 years
Progression-free survival (PFS) of FT538 in combination with daratumumab or elotuzumab in r/r MM	Defined as the time from first dose of study treatment to disease progression or relapse, or to the day of death from any cause, as determined by the investigator according to standard IMWG response criteria	Up to 15 years
Relapse-free survival (RFS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM	Defined as the time from initial CR (including CRMRD-, CR, and CRi) to hematologic relapse or death due to any cause, as determined by the investigator according to 2017 ELN criteria for AML, and defined as the duration from the start of sCR or CR until the time of relapse from sCR or CR, as determined by the investigator according to standard IMWG response criteria for MM	Up to 15 years
Event-free survival (EFS) of FT538 as monotherapy in r/r AML	defined as the time from first dose of lympho-conditioning to the date of PD, or relapse from CR or CRi, or death from any cause, according to 2017 ELN criteria	Up to 15 years
Overall survival (OS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM	defined as the time from first dose of lympho-conditioning to death from any cause	Up to 15 years
Time-to-best response of FT538 as monotherapy in r/r AML	defined as the time from first dose of lympho-conditioning to best response	Up to 15 years
Determination of the pharmacokinetics (PK) of FT538 cells in peripheral blood	The PK of FT538 in peripheral blood will be reported as the relative percentage of product (FT538) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points	Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29

Collaborators and Investigators

• Sponsor: Fate Therapeutics
• Investigators: Study Director: Fate Trial Disclosure, Fate Therapeutics, Inc

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2020
• Primary Completion (Actual): July 13, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Multiple Myeloma; AML; cellular therapy; NK cell; daratumumab; Anti-CD38; CD38; elotuzumab; allogeneic cell therapy; allogeneic cellular therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Daratumumab; Fludarabine; Elotuzumab
• Other Study ID Numbers: FT538-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No