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

• ClinicalTrials.gov Identifier: NCT05665062
• Recruitment Status: Recruiting
• First Posted: December 27, 2022
• Last Update Posted: March 21, 2024
• Sponsor: Synthekine
• Information provided by (Responsible Party): Synthekine

Tracking Information

• First Submitted Date: December 8, 2022
• First Posted Date: December 27, 2022
• Last Update Posted Date: March 21, 2024
• Actual Study Start Date: June 24, 2022
• Estimated Primary Completion Date: June 24, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2022)

• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 16, 2022)

• Objective response rate (ORR) [ Time Frame: Up to 24 months post infusion (SYNCAR-001+STK-009) ]
  The ORR to treatment with SYNCAR-001 + STK-009
• Duration of Response (DOR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to 24 months post infusion (SYNCAR-001+STK-009) ]
  The quantification of the cumulative amount of drug over time.
• Maximum Concentration (Cmax) [ Time Frame: Up to 24 months post infusion (SYNCAR-001+STK-009) ]
  To identify the maximum (peak) drug concentration dosing.
• Time of maximum concentration [ Time Frame: Up to 24 months post infusion (SYNCAR-001+STK-009) ]
  The time to reach maximum (peak) drug concentration after dosing.
• Immunogenicity [ Time Frame: 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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies
• 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
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

• Experimental: 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

  Interventions:

  • Drug: SYNCAR-001
  • Drug: STK-009
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
• Experimental: 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

  Interventions:

  • Drug: SYNCAR-001
  • Drug: STK-009

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 16, 2022): 36
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2026
• Estimated Primary Completion Date: June 24, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Operations; 650.271.9888; clinicaltrialinfo@synthekine.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05665062
• Other Study ID Numbers: STK-009-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Synthekine
• Original Responsible Party: Same as current
• Current Study Sponsor: Synthekine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Synthekine
• Verification Date: March 2024