CLL/SLL, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Indolent B-Cell Non-Hodgkin Lymphoma, Large B-cell Lymphoma, Mantle Cell Lymphoma, NHL
Conditions
Keywords
CART, CD19-CART, Chimeric antigen receptor, IL-2
Brief summary
This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies.
Detailed 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.
Interventions
DRUGSYNCAR-001
SYNCAR-001 is an autologous CD19-targeted CAR-T with co-expression of hoRb
DRUGSTK-009
STK-009 is a human orthogonal IL-2 cytokine selective for SYNCAR-001 CAR-T cells expressing hoRb
DRUGCyclophosphamide
lymphodepletion
DRUGFludarabine
lymphodepletion
Sponsors
Synthekine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) | Up to 28 days post infusion (SYNCAR-001+STK-009) | Incidence of adverse events (AEs) meeting protocol defined DLT criteria and determination of the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of STK-009 in combination with a fixed dose of SYNCAR-001 |
| Adverse events | Up to 24 months post infusion (SYNCAR-001+STK-009) | Assess the safety and tolerability of STK-009 in combination with SYNCAR-001 by review of AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 24 months post infusion (SYNCAR-001+STK-009) | The ORR to treatment with SYNCAR-001 + STK-009 |
| Duration of Response (DOR) | Up to 24 months post infusion (SYNCAR-001+STK-009) | To evaluate the duration of anti-cancer response after SYNCAR-001 + STK-009 administration. |
| Progression Free Survival (PFS) | Up to 24 months post infusion (SYNCAR-001+STK-009) | The time from the SYNCAR-001 administration date to the date of disease progression per Lugano Classification or iwCLL or death from any cause, whichever occurs earlier. |
| Area under the curve (AUC) | Up to 24 months post infusion (SYNCAR-001+STK-009) | The quantification of the cumulative amount of drug over time. |
| Maximum Concentration (Cmax) | Up to 24 months post infusion (SYNCAR-001+STK-009) | To identify the maximum (peak) drug concentration dosing. |
| Time of maximum concentration | Up to 24 months post infusion (SYNCAR-001+STK-009) | The time to reach maximum (peak) drug concentration after dosing. |
| Immunogenicity | Up to 24 months post infusion (SYNCAR-001+STK-009) | Immunogenicity will be assessed by summarizing the number of patients who develop detectable anti-STK-009 and/or anti-SYNCAR-001 anti-drug antibodies (ADAs) |
Countries
United States
Outcome results
None listed