Clinical trial NCT05182073: FT576 in Subjects With Multiple Myeloma
Official title: A Phase I Study of FT576 as Monotherapy and in Combination With Daratumumab in Subjects With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Myeloma
Keywords: 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
Lead sponsor: Fate Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-01-10
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Incidence and nature of DLTs within each dose-escalation cohort to determine the MTD or MAD
timeFrame: 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
measure: Determine the RP2D which will be based on the overall safety and anti-tumor activity among the dose escalation and dose expansion cohorts
timeFrame: From FPI to LPI's end of Cycle 1 study treatment (End of cycle is Day 29 from Day 1 FT576 infusion)
measure: Incidence, nature, and severity of adverse events
timeFrame: 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 outcomes:
measure: Objective response rate (ORR)
timeFrame: From baseline tumor assessment up to approximately 2 years after last dose of FT576
measure: Duration of response (DOR)
timeFrame: Up to 15 years
measure: Progression-free survival (PFS)
timeFrame: Up to 15 years
measure: Relapse-free survival (RFS) from complete response (CR)
timeFrame: Up to 15 years
measure: Overall survival (OS)
timeFrame: Up to 15 years
measure: Pharmacokinetics (PK) of FT576
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Denver
country: United States
facility: Scri-Cbci
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants
state: Delaware
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Saint Paul
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Medical City Dallas
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Fate Therapeutics, Inc
name: Fate Trial Disclosure
role: STUDY_DIRECTOR
References: