FT596 in Combination With R-CHOP in Subjects With B-Cell Lymphoma

Study Overview
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Brief Summary
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This is a Phase I study of FT596 in combination with two different schedules (standard or alternate) of R-CHOP in subjects with B-cell lymphoma who are previously untreated or have received no more than one prior line of treatment. The study will consist of a dose-escalation stage followed by a dose-expansion stage.

Detailed Description
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This is a Phase I study of FT596 in combination with 2 different schedules (standard or alternate) of R-CHOP in subjects with B-cell lymphoma who are previously untreated or have received no more than one prior line of treatment. The study will evaluate both the clinical benefit of FT596 when combined with R-CHOP given on a standard or alternate schedule. Subjects will be enrolled in two stages: a dose-escalation stage and a dose-expansion stage. After safety and tolerability have been assessed to define the maximum tolerated dose (MTD) (or the maximum assessed dose [MAD] in the absence of dose limiting toxicities [DLTs] defining the MTD) in the dose-escalation stage, the dose-expansion stage will further evaluate the safety and activity of FT596 in combination.

Official Title
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A Phase 1b, Open-Label, Multicenter Study of FT596 in Combination With R-CHOP in Subjects With B-Cell Lymphoma

Conditions
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Diffuse Large B Cell Lymphoma, Transformed Indolent Non-Hodgkin's Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: FT596
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone
* Drug: Rituximab
* Drug: Bendamustine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of B-cell lymphoma (BCL) as described below: Histologically documented BCL Previously untreated or no more than one prior systemic therapy for BCL At least one bi-dimensionally measurable lesion Subjects with >1 measurable lesion agreement to undergo a biopsy Capable of giving signed informed consent Age ≥ 18 years old Stated willingness to comply with study procedures through study duration Contraception use for women and men as defined in the protocol Negative serum pregnancy test within 7 days of treatment for women Key Exclusion Criteria: Prior anthracycline therapy Females who are pregnant or breastfeeding Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2 Evidence of insufficient organ function Currently receiving or likely to receive systemic immunosuppressive therapy Receipt of 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 Positive HIV test Positive Hepatitis B (HBV) or Hepatitis C (HCV) test Live vaccine <6 weeks prior to start of conditioning Allergy to human albumin or dimethyl sulfoxide (DMSO)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be assigned to one of 2 treatment regimens corresponding to different schedules (standard or alternate) of R-CHOP
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A (FT596 in combination with standard schedule R-CHOP)<br>FT596 in combination with standard schedule R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on Day 1; prednisone on Days 1-5; and FT596 on Day 8) for a total of six 21-day cycles. | Drug: FT596<br>* Dosing to be initiated at a dose no higher than highest tolerable dose in study FT596-101, intravenously<br>Drug: Cyclophosphamide<br>* 750 mg/m^2 intravenously<br>Drug: Doxorubicin<br>* 50 mg/m^2 intravenously<br>Drug: Vincristine<br>* 1.4 mg/m^2 (maximum dose 2 mg) intravenously<br>Drug: Prednisone<br>* 100 mg orally<br>Drug: Rituximab<br>* 375 mg/m^2 intravenously<br>* Other names: Ruxience;Drug: Bendamustine<br>* 90 mg/m^2 IV infusion<br>* Other names: Treanda;|
| Experimental: Regimen B (FT596 in combination with alternate schedule R-CHOP)<br>FT596 in combination with alternate schedule R-CHOP (prednisone on Days 1-5; rituximab, cyclophosphamide, doxorubicin, and vincristine on Day 5; and FT596 on Day 8) for a total of six 21-day cycles | Drug: FT596<br>* Dosing to be initiated at a dose no higher than highest tolerable dose in study FT596-101, intravenously<br>Drug: Cyclophosphamide<br>* 750 mg/m^2 intravenously<br>Drug: Doxorubicin<br>* 50 mg/m^2 intravenously<br>Drug: Vincristine<br>* 1.4 mg/m^2 (maximum dose 2 mg) intravenously<br>Drug: Prednisone<br>* 100 mg orally<br>Drug: Rituximab<br>* 375 mg/m^2 intravenously<br>* Other names: Ruxience;Drug: Bendamustine<br>* 90 mg/m^2 IV infusion<br>* Other names: Treanda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities within each dose escalation cohort |  | Day 21 | 
| Nature of dose-limiting toxicities within each dose escalation cohort |  | Day 21 | 
| Incidence, nature, and severity of adverse events (AEs) of FT596 in combination with R-CHOP in B-cell lymphoma previously untreated or no more than one previous line of therapy with severity determined according to NCI CTCAE, v5.0 |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed complete response (CR) | Proportion of subjects who achieve a complete response (CR) per Lugano 2014 classification | Up to 2 years | 
| Investigator-assessed objective-response rate (ORR) | Proportion of subjects who achieve a partial response (PR) or complete response (CR) per Lugano 2014 classification | Up to 2 years | 
| Investigator-assessed duration of response (DOR) | Duration from the first occurrence of a documented objective response until the time of disease progression or relapse, or death from any cause, whichever occurs first, per Lugano 2014 classification | Up to 15 years | 
| Investigator-assessed duration of complete response (DoCR) | Duration from the first occurrence of a documented complete response (CR), per Lugano 2014 classification until the time of disease progression or relapse, or death from any cause, whichever occurs first | Up to 15 years | 
| Progression-free survival (PFS) | Time from first dose of study treatment to progressive disease (PD), or to the day of death for any reason, whichever occurs earlier, based on Lugano 2014 classification | Up to 15 years | 
| Overall survival (OS) | Time from first dose of study treatment to death from any cause | Up to 15 years | 
| Area Under the Plasma Concentration Time Curve (AUC) of FT596 | Assessed by the detection of FT596 in peripheral blood following FT596 administration. | Cycles 1-6 (each cycle is 28 days): Days 1,8,11,15,18; and Post-Treatment Week 1, Week 2, Week 4, and Week 8 | 
| Maximum Plasma Concentration (Cmax) of FT596 | Assessed by the detection of FT596 in peripheral blood following FT596 administration. | Cycles 1-6 (each cycle is 28 days): Days 1,8,11,15,18; and Post-Treatment Week 1, Week 2, Week 4, and Week 8 |