FT576 in Subjects With Multiple Myeloma

A Phase I Study of FT576 as Monotherapy and in Combination With Daratumumab in Subjects With Relapsed/Refractory Multiple Myeloma

This is a Phase I dose-finding study of FT576 as monotherapy and in combination with the monoclonal antibody daratumumab in multiple myeloma (MM). The study will consist of a dose-escalation stage and an expansion stage.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Myeloma
• Intervention / Treatment: Drug: FT576 (Allogenic CAR NK cells with BCMA expression); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Daratumumab; Drug: Bendamustine

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fate Trial Disclosure; Phone Number: 866-875-1800; Email: FateTrialDisclosure@fatetherapeutics.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Recruiting
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Scri-Cbci
  • Delaware
    • Newark, Delaware, United States, 19713
      • Recruiting
      • Medical Oncology Hematology Consultants
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
  • Minnesota
    • Saint Paul, Minnesota, United States, 55108
      • Recruiting
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45226
      • Recruiting
      • Oncology Hematology Care, Inc
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology - Nashville
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Texas Oncology-Medical City Dallas
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

• Abbreviated inclusion criteria:

Diagnosis of r/r MM with measurable disease by at least one of the following:

• Serum M-protein ≥1.0 g/dL
• Urine M-protein ≥200 mg/24 hours
• Involved serum free light chain level ≥10 mg/dL, with an abnormal kappa-lambda ratio if the serum M-protein <1.0 g/dL and/or urine M-protein <200 mg/24 hours
• Regimens A and A1: MM relapsed or progressed after ≥3 prior approved therapies, including an IMiD, proteosome inhibitor, and anti-CD38 mAb
• Regimens B and B1: MM relapsed or progressed after ≥2 prior approved therapies, including an IMiD and proteosome inhibitor

Note: for all Regimens, prior BCMA CAR T-cell therapy and BCMA-targeted therapy (e.g., bi-specific engagers or antibody-drug conjugates) is allowed

* Abbreviated exclusion criteria:

Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2

Evidence of insufficient hematologic function:

• ANC <1000/µL without growth factor support ≤7 days prior to measurement
• Platelet count <75,000/µL without platelet transfusion ≤72 hours prior to measurement

Evidence of insufficient organ function

• CrCL <50 ml/min by Cockcroft-Gault or other institutional method
• T bilirubin >1.5x ULN, except for Gilbert's syndrome
• AST >3x ULN or ALT >3x ULN, unless directly due to underlying malignancy
• O2 sat <92% on room air

Clinically significant cardiovascular disease:

• Myocardial infarction within 6 months of first treatment
• Unstable angina or CHF of NYHA Grade 2 or higher
• Cardiac EF <40%

Subjects with active central nervous system (CNS) , including leptomeningeal disease. Subjects with prior CNS involvement may be enrolled into the study if effective treatment of their CNS disease was completed at least 3 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging.

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

Currently receiving or likely to require immunosuppressive therapy (e.g., prednisone >5 mg daily) for any reason during the treatment period, with the exception of corticosteroids.

Clinically significant infections, including:

• HIV positive by serology
• HBV positive by serology or PCR
• HCV positive by serology or PCR

Live vaccine <6 weeks prior to start of conditioning

Receipt of an allograft organ transplant

Ongoing requirement for systemic graft -versus-host disease therapy

Plasma cell leukemia defined as a plasma cell count >2000/mm^3

Prior malignancy (other than current indication including any antecedent hematologic disorder) within the 2 years prior to enrollment except for the following: basal or squamous cell carcinomas of the skin, carcinoma in situ of the cervix or breast treated with curative intent, or localized prostate cancer treated with curative intent, or malignancy that, in the opinion of the investigator and Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years.

Washout periods from prior therapies:

• For all subjects (Regimens A, A1, B and B1), receipt of the following: Chemotherapy, or radiation therapy, except for palliative purposes, within 14 days prior to the first dose of FT576 (Day 1) or five half-lives, whichever is shorter; Investigational therapy within 30 days prior to the first dose of FT576 study treatment or five half-lives, whichever is shorter; Biologic therapy (except for anti-CD38 mAbs in Regimen B and B1), including autologous cellular immunotherapy (e.g. CAR-T/ CAR-NK), antibody-drug conjugates or bi-specific immune-cell engaging antibody within 30 days prior to first dose of FT576 (Day 1) or half -lives whichever is shorter. prior allogenic HSCT or allogenic CAR-T/CAR-NK within 6 months of first dose of FT576 (Day1).
• For subjects in Regimens B and B1 only, receipt of the following: Anti-CD38 therapy alone or in combination within 3 months prior to the start of daratumumab

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regimen A; FT576 single dose monotherapy in subjects with r/r MM	Drug: FT576 (Allogenic CAR NK cells with BCMA expression); Experimental Interventional Therapy: FT576 comprises allogeneic natural killer (NK) cells, derived from a clonal, CD38-knockout, human-induced pluripotent stem cell line (iPSC) that expresses anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR), high-affinity, non-cleavable CD16 (hnCD16), and IL-15/IL-15 receptor fusion protein (IL-15RF).; Drug: Cyclophosphamide; Conditioning Agent; Drug: Fludarabine; Conditioning Agent; Drug: Bendamustine; Conditioning Agent; Other Names: Treanda; Bendeka
Experimental: Regimen A1; FT576 multiple dose monotherapy in subjects with r/r MM	Drug: FT576 (Allogenic CAR NK cells with BCMA expression); Experimental Interventional Therapy: FT576 comprises allogeneic natural killer (NK) cells, derived from a clonal, CD38-knockout, human-induced pluripotent stem cell line (iPSC) that expresses anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR), high-affinity, non-cleavable CD16 (hnCD16), and IL-15/IL-15 receptor fusion protein (IL-15RF).; Drug: Cyclophosphamide; Conditioning Agent; Drug: Fludarabine; Conditioning Agent; Drug: Bendamustine; Conditioning Agent; Other Names: Treanda; Bendeka
Experimental: Regimen B; FT576 single dose in combination with daratumumab in subjects with r/r MM	Drug: FT576 (Allogenic CAR NK cells with BCMA expression); Experimental Interventional Therapy: FT576 comprises allogeneic natural killer (NK) cells, derived from a clonal, CD38-knockout, human-induced pluripotent stem cell line (iPSC) that expresses anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR), high-affinity, non-cleavable CD16 (hnCD16), and IL-15/IL-15 receptor fusion protein (IL-15RF).; Drug: Cyclophosphamide; Conditioning Agent; Drug: Fludarabine; Conditioning Agent; Drug: Daratumumab; Anti-CD38 Monoclonal Antibody; Other Names: Darzalex; Darzalex Faspro; Drug: Bendamustine; Conditioning Agent; Other Names: Treanda; Bendeka
Experimental: Regimen B1; FT576 multiple dose in combination with daratumumab in subjects with r/r MM	Drug: FT576 (Allogenic CAR NK cells with BCMA expression); Experimental Interventional Therapy: FT576 comprises allogeneic natural killer (NK) cells, derived from a clonal, CD38-knockout, human-induced pluripotent stem cell line (iPSC) that expresses anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR), high-affinity, non-cleavable CD16 (hnCD16), and IL-15/IL-15 receptor fusion protein (IL-15RF).; Drug: Cyclophosphamide; Conditioning Agent; Drug: Fludarabine; Conditioning Agent; Drug: Daratumumab; Anti-CD38 Monoclonal Antibody; Other Names: Darzalex; Darzalex Faspro; Drug: Bendamustine; Conditioning Agent; Other Names: Treanda; Bendeka

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and nature of DLTs within each dose-escalation cohort to determine the MTD or MAD	Cycle 1 Day -5 to Day 29 for Regimen A and A1; Cycle 1 Day -11 to Day 29 (each cycle is 40 days) for Regimen B and B1
Determine the RP2D which will be based on the overall safety and anti-tumor activity among the dose escalation and dose expansion cohorts	From FPI to LPI's end of Cycle 1 study treatment (End of cycle is Day 29 from Day 1 FT576 infusion)
Incidence, nature, and severity of adverse events	Cycle 1 Day -5 to Day 29 for Regimen A and A1; Cycle 1 Day -11 to Day 29 (each cycle is 40 days) for Regimen B and B1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Proportion of subjects with a best overall response of sCR, CR, VGPR, or PR, as determined by the investigator according to standard IMWG response criteria	From baseline tumor assessment up to approximately 2 years after last dose of FT576
Duration of response (DOR)	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)	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) from complete response (CR)	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	Up to 15 years
Overall survival (OS)	Time from first dose of study treatment to death from any cause	Up to 15 years
Pharmacokinetics (PK) of FT576	Concentration of FT576 in peripheral blood following FT576 administration	From Baseline to PTFU visit of last cycle on the study treatment (End of cycle is Day 29 from Day 1 FT576 infusion of this cycle)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• ASH Dec 2020 Abstract

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): February 1, 2040

Study Registration Dates

• First Submitted: October 15, 2021
• First Submitted That Met QC Criteria: January 5, 2022
• First Posted (Actual): January 10, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; cellular therapy; anti-CD38 monoclonal antibody; BCMA; daratumumab; relapsed/refractory multiple myeloma; CAR NK cell; allogeneic natural killer cells; chimeric antigen receptor (CAR); anti-B-cell maturation antigen (BCMA); natural killer (NK) cell
• 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; 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; Bendamustine Hydrochloride; Daratumumab; Antibodies, Monoclonal; Fludarabine
• Other Study ID Numbers: FT576-101

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