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

Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05665062
• Other study ID #: STK-009-101
• Status: Recruiting
• Phase: Phase 1
• Start date: June 24, 2022
• Est. completion date: November 2026

Study information

• Verified date: March 2024
• Source: Synthekine
• Contact: Clinical Operations
• Phone: 650.271.9888
• Email: clinicaltrialinfo[@]synthekine.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: November 2026
• Est. primary completion date: June 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• SYNCAR-001
SYNCAR-001 is an autologous CD19-targeted CAR-T with co-expression of hoRb
• STK-009
STK-009 is a human orthogonal IL-2 cytokine selective for SYNCAR-001 CAR-T cells expressing hoRb
• Cyclophosphamide
lymphodepletion
• Fludarabine
lymphodepletion

Locations

Country	Name	City	State
United States	Roswell Park	Buffalo	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Synthekine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Objective response rate (ORR)	The ORR to treatment with SYNCAR-001 + STK-009	Up to 24 months post infusion (SYNCAR-001+STK-009)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Maximum Concentration (Cmax)	To identify the maximum (peak) drug concentration dosing.	Up to 24 months post infusion (SYNCAR-001+STK-009)
Secondary	Time of maximum concentration	The time to reach maximum (peak) drug concentration after dosing.	Up to 24 months post infusion (SYNCAR-001+STK-009)
Secondary	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)