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
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 36
- Locations
- 6
- Primary Endpoint
- Dose Limiting Toxicities (DLTs)
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
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
Arms & Interventions
SYNCAR-001 + STK-009 Cohort A
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
Intervention: SYNCAR-001 (Drug)
SYNCAR-001 + STK-009 Cohort A
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
Intervention: STK-009 (Drug)
SYNCAR-001 + STK-009 Cohort A
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
Intervention: Cyclophosphamide (Drug)
SYNCAR-001 + STK-009 Cohort A
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
Intervention: Fludarabine (Drug)
SYNCAR-001 + STK-009 Cohort B
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
Intervention: STK-009 (Drug)
SYNCAR-001 + STK-009 Cohort B
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
Intervention: SYNCAR-001 (Drug)
Outcomes
Primary Outcomes
Dose Limiting Toxicities (DLTs)
Time Frame: 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
Time Frame: 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 Outcomes
- Objective response rate (ORR)(Up to 24 months post infusion (SYNCAR-001+STK-009))
- Duration of Response (DOR)(Up to 24 months post infusion (SYNCAR-001+STK-009))
- Progression Free Survival (PFS)(Up to 24 months post infusion (SYNCAR-001+STK-009))
- Area under the curve (AUC)(Up to 24 months post infusion (SYNCAR-001+STK-009))
- Maximum Concentration (Cmax)(Up to 24 months post infusion (SYNCAR-001+STK-009))
- Time of maximum concentration(Up to 24 months post infusion (SYNCAR-001+STK-009))
- Immunogenicity(Up to 24 months post infusion (SYNCAR-001+STK-009))