FT576 in Subjects With Multiple Myeloma

Fate Therapeutics

Status and phase: Active, not recruiting; Phase 1

Conditions: Multiple Myeloma; Myeloma

Treatments: Drug: Cyclophosphamide; Drug: Bendamustine; Drug: Fludarabine; Drug: Daratumumab; Drug: FT576 (Allogenic CAR NK cells with BCMA expression)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05182073

FT576-101

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 - A4 only: MM relapsed or progressed after ≥3 prior approved therapies, including an IMiD, proteosome inhibitor, and anti-CD38 mAb
• Regimens B - B4 only: 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 inhaled 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:

• 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 (e.g., anti-CD38 mAbs or anti-SLAMF7 monoclonal antibodies), 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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 4 patient groups

Regimens A-A4

Experimental group

Description:

FT576 single dose monotherapy in subjects with r/r MM

Treatment:

Drug: FT576 (Allogenic CAR NK cells with BCMA expression)

Drug: Fludarabine

Drug: Bendamustine

Drug: Cyclophosphamide

Regimen A1

Experimental group

Description:

FT576 multiple dose monotherapy in subjects with r/r MM

Treatment:

Drug: FT576 (Allogenic CAR NK cells with BCMA expression)

Drug: Fludarabine

Drug: Bendamustine

Drug: Cyclophosphamide

Regimens B-B4

Experimental group

Description:

FT576 single dose in combination with daratumumab in subjects with r/r MM

Treatment:

Drug: FT576 (Allogenic CAR NK cells with BCMA expression)

Drug: Daratumumab

Drug: Fludarabine

Drug: Bendamustine

Drug: Cyclophosphamide

Regimen B1

Experimental group

Description:

FT576 multiple dose in combination with daratumumab in subjects with r/r MM

Treatment:

Drug: FT576 (Allogenic CAR NK cells with BCMA expression)

Drug: Daratumumab

Drug: Fludarabine

Drug: Bendamustine

Drug: Cyclophosphamide