This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
SYNCAR-001 is an autologous CD19-targeted CAR-T with co-expression of hoRb
STK-009 is a human orthogonal IL-2 cytokine selective for SYNCAR-001 CAR-T cells expressing hoRb
lymphodepletion
City of Hope
Duarte, California, United States
Roswell Park
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Cleveland Clinic
Cleveland, Ohio, United States
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
Time frame: 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
Time frame: Up to 24 months post infusion (SYNCAR-001+STK-009)
Objective response rate (ORR)
The ORR to treatment with SYNCAR-001 + STK-009
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 24 months post infusion (SYNCAR-001+STK-009)
Maximum Concentration (Cmax)
To identify the maximum (peak) drug concentration dosing.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
lymphodepletion
Time frame: Up to 24 months post infusion (SYNCAR-001+STK-009)
Time of maximum concentration
The time to reach maximum (peak) drug concentration after dosing.
Time frame: 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)
Time frame: Up to 24 months post infusion (SYNCAR-001+STK-009)