FT596 as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies

Conditions

Chronic Lymphocytic Leukemia, Lymphoma, B-Cell

Keywords

Lymphoma, Leukemia

Brief summary

This is a Phase I dose-finding study of FT596 as monotherapy and in combination with Rituximab or Obinutuzumab in subjects with relapsed/refractory B-cell Lymphoma or Chronic Lymphocytic Leukemia. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Ghobadi A, Bachanova V, Patel K, Park JH, Flinn I, Riedell PA, Bachier C, Diefenbach CS, Wong C, Bickers C, Wong L, Patel D, Goodridge J, Denholt M, Valamehr B, Elstrom RL, Strati P.

2025-01-0156 citations

10.1016/s0140-6736(24)02462-0

Safety and Efficacy of FT596, a First-in-Class, Multi-Antigen Targeted, Off-the-Shelf, iPSC-Derived CD19 CAR NK Cell Therapy in Relapsed/Refractory B-Cell Lymphoma

Veronika Bachanová, Armin Ghobadi, Krish Patel, Jae H. Park, Ian W. Flinn et al. (15 authors)

Blood2021-11-0577 citations

10.1182/blood-2021-151185

Off-the-Shelf, Multiplexed-Engineered iPSC-Derived NK Cells Mediate Potent Multi-Antigen Targeting of B-Cell Malignancies with Reduced Cytotoxicity Against Healthy B Cells

Frank Cichocki, Jode Goodridge, Ryan Bjordahl, Svetlana Gaidarova, Sajid Mahmood et al. (21 authors)

Blood2021-11-059 citations

10.1182/blood-2021-148654

Initial Clinical Activity of FT596, a First-in-Class, Multi-Antigen Targeted, Off-the-Shelf, iPSC-Derived CD19 CAR NK Cell Therapy in Relapsed/Refractory B-Cell Lymphoma

Veronika Bachanová, Zuzan Caycı, Dixie Lewis, Joseph Maakaron, Murali Janakiram et al. (12 authors)

Blood2020-11-0436 citations

10.1182/blood-2020-141606

Interventions

DRUGBendamustine

Conditioning agent

DRUGFT596

Experimental Interventional Therapy

DRUGCyclophosphamide

Lympho-conditioning agent

DRUGFludarabine

Lympho-conditioning agent

DRUGRituximab

Monoclonal Antibody

DRUGObinutuzumab

Monoclonal Antibody

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

Key Inclusion Criteria: Diagnosis of B-cell lymphoma or CLL as described below: B-Cell Lymphoma: * Histologically documented lymphomas expected to express CD19 and CD20 * Relapsed/refractory disease following prior systemic immunochemotherapy regimen Chronic Lymphocytic Leukemia (CLL): * Diagnosis of CLL per iwCLL guidelines * Relapsed/refractory disease following at least two prior systemic treatment regimens ALL SUBJECTS: * Capable of giving signed informed consent * Age ≥ 18 years old * Stated willingness to comply with study procedures and duration * Contraceptive use for women and men as defined in the protocol Key

Exclusion criteria

ALL SUBJECTS: * Females who are pregnant or breastfeeding * Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2 * Body weight \<50 kg * Evidence of insufficient organ function * Receipt therapy within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Day 1 * Currently receiving or likely to require systemic immunosuppressive therapy * Prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic GvHD therapy * Receipt of an allograft organ transplant * Known active central nervous system (CNS) involvement by malignancy * Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease * Clinically significant cardiovascular disease * Known HIV infection * Known active Hepatitis B (HBV) or Hepatitis C (HCV) infection * Live vaccine \<6 weeks prior to start of lympho-conditioning * Known allergy to albumin (human) or DMSO

Design outcomes

Primary

Measure	Time frame
Incidence of dose-limiting toxicities within each dose level cohort	Day 29
Nature of dose-limiting toxicities within each dose level cohort	Day 29
Incidence, nature, and severity of adverse events (AEs) of FT596 as monotherapy and in combination with rituximab or obinutuzumab in r/r B-cell lymphomas and r/r chronic lymphocytic leukemia, with severity determined according to NCI CTCAE, v5.0	Up to 15 years

Secondary

Measure	Time frame	Description
Progression-free survival (PFS)	Up to 15 years	Defined as the time from from first dose of lympho-conditioning to progressive disease (PD), or to the day of death for any reason, whichever occurs earlier, based on Lugano 2014 classification for lymphomas or revised iwCLL guidelines for CLL
Investigator-assessed objective-response rate (ORR)	From baseline tumor assessment up to approximately 2 years after last dose of FT596	Proportion of subjects who achieve a partial response (PR) or complete response (CR) per Lugano 2014 classification for lymphomas, a partial remission (PR) or complete remission (CR) per revised iwCLL guidelines for CLL.
The pharmacokinetics of FT596 in peripheral blood will be reported as the relative percentage of product (FT596) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points	Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29	—
Overall survival (OS), defined as the time from first dose of lympho-conditioning to death from any cause.	Up to 15 years	—
Investigator-assessed duration of objective response (DOR)	Up to 15 years	Defined as the duration from the first occurrence of a documented objective response (DOR) until the time of disease progression or relapse, or death from any cause, whichever occurs first, per Lugano 2014 classification for lymphomas or revised iwCLL guidelines for CLL.
Investigator-assessed duration of complete response (DoCR)	Up to 15 years	Defined as the duration from the first occurrence of a documented complete response (CR) per Lugano 2014 classification for lymphomas or complete remission (CR) per revised iwCLL guidelines for CLL, until the time of disease progression or relapse, or death from any cause, whichever occurs first.

Countries

United States

Outcome results

None listed