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

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

Detailed Description
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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 dose escalation design followed by a dose extension phase at the recommended phase 2 dose (RP2D)

Official Title
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A Phase 1 Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001 + STK-009) in Subjects With Relapsed or Refractory CD19+ Hematologic Malignancies

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

Intervention / Treatment
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* Drug: SYNCAR-001
* Drug: STK-009
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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Selected Inclusion Criteria: Histologically confirmed relapsed/refractory hematologic malignancies, including Chronic Lymphocytic Lymphoma (CLL/SLL) and selected Non-Hodgkin's Lymphoma (NHL) Prior or current documentation of CD19 expression or high likelihood of CD19 expression based on disease histology 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: Prior CD19 directed therapy including CD19 CARTs Prior allogeneic hematopoietic stem cell transplant within 6 months of enrollment Prior autologous hematopoietic stem cell transplant within 6 weeks of enrollment. Presence of GVHD

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYNCAR-001 + STK-009<br>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 extension: 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 | Drug: SYNCAR-001<br>* SYNCAR-001 is an autologous CD19-targeted CAR-T with co-expression of hoRb<br>Drug: STK-009<br>* STK-009 is a human orthogonal IL-2 cytokine selective for SYNCAR-001 CAR-T cells expressing hoRb<br>Drug: Cyclophosphamide<br>* lymphodepletion<br>Drug: Fludarabine<br>* lymphodepletion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLTs) | 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 | Up to 28 days post infusion (SYNCAR-001+STK-009) | 
| Adverse events | Assess the safety and tolerability of STK-009 in combination with SYNCAR-001 by review of AEs | Up to 24 months post infusion (SYNCAR-001+STK-009) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The ORR to treatment with SYNCAR-001 + STK-009 | Up to 24 months post infusion (SYNCAR-001+STK-009) | 
| Duration of Response (DOR) | To evaluate the duration of anti-cancer response after SYNCAR-001 + STK-009 administration. | Up to 24 months post infusion (SYNCAR-001+STK-009) | 
| Progression Free Survival (PFS) | 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. | Up to 24 months post infusion (SYNCAR-001+STK-009) | 
| Area under the curve (AUC) | The quantification of the cumulative amount of drug over time. | Up to 24 months post infusion (SYNCAR-001+STK-009) | 
| Maximum Concentration (Cmax) | To identify the maximum (peak) drug concentration dosing. | Up to 24 months post infusion (SYNCAR-001+STK-009) | 
| Time of maximum concentration | The time to reach maximum (peak) drug concentration after dosing. | Up to 24 months post infusion (SYNCAR-001+STK-009) | 
| Immunogenicity | 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) | Up to 24 months post infusion (SYNCAR-001+STK-009) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CART, CD19-CART, Chimeric antigen receptor, IL-2