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

Phase 1

Recruiting

• Conditions: CLL/SLL; NHL; Mantle Cell Lymphoma; Follicular Lymphoma; Large B-cell Lymphoma; Indolent B-Cell Non-Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma
• Interventions: Drug: SYNCAR-001; Drug: STK-009; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT05665062
• Lead Sponsor: Synthekine

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.

Study Timeline

• Study Start: 2022-06-24
• Study First Submitted: 2022-12-08
• Study First Submitted QC: 2022-12-16
• Study First Posted: 2022-12-27
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-19
• Last Update Posted: 2024-03-21
• Primary Completion: 2026-06-24
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SYNCAR-001 + STK-009 Cohort A	SYNCAR-001	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
SYNCAR-001 + STK-009 Cohort A	STK-009	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
SYNCAR-001 + STK-009 Cohort A	Cyclophosphamide	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
SYNCAR-001 + STK-009 Cohort B	STK-009	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
SYNCAR-001 + STK-009 Cohort B	SYNCAR-001	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
SYNCAR-001 + STK-009 Cohort A	Fludarabine	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Objective response rate (ORR)	Up to 24 months post infusion (SYNCAR-001+STK-009)	The ORR to treatment with SYNCAR-001 + STK-009
Maximum Concentration (Cmax)	Up to 24 months post infusion (SYNCAR-001+STK-009)	To identify the maximum (peak) drug concentration dosing.
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.
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)

Trial Locations

Locations (4)

Roswell Park; 🇺🇸 Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

City of Hope; 🇺🇸 Duarte, California, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States