Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies

Synthekine

Status and phase: Active, not recruiting; Phase 1

Conditions: CLL/SLL; NHL; Indolent B-Cell Non-Hodgkin Lymphoma; Large B-cell Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma

Treatments: Drug: STK-009; Drug: Cyclophosphamide; Drug: SYNCAR-001; Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05665062

STK-009-101

Details and patient eligibility

About

This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies.

Full description

SYNCAR-001 + STK-009 is a 2-component human orthogonal (ho) IL-2 receptor-ligand cell therapy consisting of (1) SYNCAR-001, a CD19-directed chimeric antigen receptor T cell (CAR-T) co-expressing an engineered IL-2 beta receptor (hoRb); and (2) STK-009, an engineered pegylated IL-2 cytokine (hoIL-2) selective for hoRb. The study will follow a 3+3 design during dose escalation. Cohort A will enroll subjects to SYNCAR-001 + STK-009 with lymphodepletion. At Dose Level 3, a separate dose escalation cohort will be introduced to enroll subjects to SYNCAR-001 + STK-009 without lymphodepletion (Cohort B). Subsequent dose expansions will enroll subjects at the RP2D for each cohort.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Selected Inclusion Criteria:

1. Histologically confirmed relapsed/refractory hematologic malignancies, including Chronic Lymphocytic Lymphoma (CLL/SLL) and selected Non-Hodgkin's Lymphoma (NHL)
2. Prior or current documentation of CD19 expression or high likelihood of CD19 expression based on disease histology
3. No signs of symptoms of central nervous system (CNS) disease or detectable evidence of CNS or meningeal disease on magnetic resonance imaging (MRI) at the time of screening

Selected Exclusion Criteria:

1. Prior CD19 directed therapy including CD19 CARTs
2. Prior allogeneic hematopoietic stem cell transplant within 6 months of enrollment
3. Prior autologous hematopoietic stem cell transplant within 6 weeks of enrollment.
4. Presence of GVHD

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 2 patient groups

SYNCAR-001 + STK-009 Cohort A

Experimental group

Description:

Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with repeated sequential ascending doses of STK-009 subcutaneously (SC) Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with repeated doses of STK-009 SC at the RP2D

Treatment:

Drug: Fludarabine

Drug: SYNCAR-001

Drug: Cyclophosphamide

Drug: STK-009

SYNCAR-001 + STK-009 Cohort B

Experimental group

Description:

Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with repeated sequential ascending doses of STK-009 subcutaneously (SC) Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with repeated doses of STK-009 SC at the RP2D

Treatment:

Drug: SYNCAR-001

Drug: STK-009