FT576 in Subjects With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05182073
• Other study ID #: FT576-101
• Status: Recruiting
• Phase: Phase 1
• Start date: November 24, 2021
• Est. completion date: February 2040

Study information

• Verified date: March 2024
• Source: Fate Therapeutics
• Contact: Fate Trial Disclosure
• Phone: 866-875-1800
• Email: FateTrialDisclosure[@]fatetherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: February 2040
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Myeloma
• Neoplasms, Plasma Cell

Intervention

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).
• Cyclophosphamide
Conditioning Agent
• Fludarabine
Conditioning Agent
• Daratumumab
Anti-CD38 Monoclonal Antibody
• Bendamustine
Conditioning Agent

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Roswell Park	Buffalo	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Oncology Hematology Care, Inc	Cincinnati	Ohio
United States	Texas Oncology-Medical City Dallas	Dallas	Texas
United States	Scri-Cbci	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Indiana University	Indianapolis	Indiana
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Medical Oncology Hematology Consultants	Newark	Delaware
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Washington University	Saint Louis	Missouri
United States	University of Minnesota	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	Time from first dose of study treatment to death from any cause	Up to 15 years
Secondary	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)

External Links

•   ASH Dec 2020 Abstract