FT576 in Subjects With Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT05182073
• Recruitment Status: Recruiting
• First Posted: January 10, 2022
• Last Update Posted: May 2, 2022
• Sponsor: Fate Therapeutics
• Information provided by (Responsible Party): Fate Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Myeloma	Drug: FT576 (Allogenic CAR NK cells with BCMA expression); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Daratumumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 168 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of FT576 as Monotherapy and in Combination With Daratumumab in Subjects With Relapsed/Refractory Multiple Myeloma
• Actual Study Start Date: November 24, 2021
• Estimated Primary Completion Date: September 2024
• Estimated Study Completion Date: February 2040

Arms and Interventions

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
Experimental: Regimen A1; FT576 fractionated 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
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
Experimental: Regimen B1; FT576 fractionated 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

Outcome Measures

Primary Outcome Measures :

1. Incidence and nature of DLTs within each dose-escalation cohort to determine the MTD or MAD [ Time Frame: Cycle 1 Day -11 to Day 29 (each cycle is 40 days) ]
2. Determine the RP2D which will be based on the overall safety and anti-tumor activity among the dose escalation and dose expansion cohorts [ Time Frame: From FPI to LPI's end of Cycle 1 study treatment (End of cycle is Day 29 from Day 1 FT576 infusion) ]
3. Incidence, nature, and severity of adverse events [ Time Frame: Cycle 1 Day -11 to Day 29 (each cycle is 40 days) ]

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: From baseline tumor assessment up to approximately 2 years after last dose of FT576 ]
   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
2. Duration of response (DOR) [ Time Frame: Up to 15 years ]
   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
3. Progression-free survival (PFS) [ Time Frame: Up to 15 years ]
   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
4. Relapse-free survival (RFS) from complete response (CR) [ Time Frame: Up to 15 years ]
   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
5. Overall survival (OS) [ Time Frame: Up to 15 years ]
   Time from first dose of study treatment to death from any cause
6. Pharmacokinetics (PK) of FT576 [ Time Frame: From Baseline to end of last cycle of the study treatment (End of cycle is Day 29 from Day 1 FT576 infusion of this cycle) ]
   Concentration of FT576 in peripheral blood following FT576 administration

Eligibility Criteria

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

Criteria

• 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 PI

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 prior central nervous system (CNS) involvement of MM must have completed effective treatment of their CNS disease 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 systemic 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

Prior allogeneic HSCT or allogeneic CAR T/CAR NK within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host therapy

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

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 Day 1 or five half-lives, whichever is shorter; Investigational therapy within 30 days prior to the first dose of study treatment or five half-lives, whichever is shorter; Biologic therapy (except for anti-CD38 mAbs), including antibody-drug conjugates or bi-specific immune-cell engaging antibody within 30 days prior to Day 1
• 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

Contacts and Locations

Contacts

Contact: Smriti Rai; 8588751800; clinical@fatetherapeutics.com

Contact: Dennis Hazekamp; 8588751800; clinical@fatetherapeutics.com

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35249

United States, Colorado

Colorado Blood Cancer Institute; Recruiting

Denver, Colorado, United States, 80218

United States, Indiana

Indiana University Melvin and Bern Simon Comprehensive Cancer Center; Recruiting

Indianapolis, Indiana, United States, 46202

United States, Tennessee

Tennessee Oncology - Nashville; Recruiting

Nashville, Tennessee, United States, 37203

United States, Wisconsin

Froedtert Hospital, Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Fate Therapeutics

Investigators

• Study Director: Ted Shih, PharmD; Fate Therapeutics, Inc

More Information

Additional Information:

ASH Dec 2020 Abstract 

• Responsible Party: Fate Therapeutics
• ClinicalTrials.gov Identifier: NCT05182073
• Other Study ID Numbers: FT576-101
• First Posted: January 10, 2022
• Last Update Posted: May 2, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Fate Therapeutics:

Multiple Myeloma; daratumumab; CAR NK cell; cellular therapy; relapsed/refractory multiple myeloma; allogeneic natural killer cells; anti-CD38 monoclonal antibody; chimeric antigen receptor (CAR); BCMA; anti-B-cell maturation antigen (BCMA); natural killer (NK) cell

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Cyclophosphamide; Fludarabine; Daratumumab; Antibodies, Monoclonal; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists