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

• Sponsor: Synthekine (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05665062
• Collaborator: (none)
• Enrollment: 36
• Locations: 5
• Arm: 1
• Anticipated Duration (Months): 46
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
CLL/SLL; NHL; Mantle Cell Lymphoma; Follicular Lymphoma; Large B-cell Lymphoma; Indolent B-Cell Non-Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma	Drug: SYNCAR-001; Drug: STK-009; Drug: Cyclophosphamide; Drug: Fludarabine	Phase 1

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 dose escalation design followed by a dose extension phase at the recommended phase 2 dose (RP2D)

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Jan 1, 2023
• Anticipated Primary Completion Date: Jun 1, 2024
• Anticipated Study Completion Date: Nov 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SYNCAR-001 + 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 extension: 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	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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

1. Objective response rate (ORR) [Up to 24 months post infusion (SYNCAR-001+STK-009)]

   The ORR to treatment with SYNCAR-001 + STK-009

2. 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.

3. 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.

4. 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.

5. Maximum Concentration (Cmax) [Up to 24 months post infusion (SYNCAR-001+STK-009)]

   To identify the maximum (peak) drug concentration dosing.

6. Time of maximum concentration [Up to 24 months post infusion (SYNCAR-001+STK-009)]

   The time to reach maximum (peak) drug concentration after dosing.

7. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Roswell Park	Buffalo	New York	United States	14263
3	Columbia University Irving Medical Center	New York	New York	United States	10032
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Synthekine

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Synthekine
• ClinicalTrials.gov Identifier: NCT05665062
• Other Study ID Numbers: STK-009-101
• First Posted: Dec 27, 2022
• Last Update Posted: Jan 13, 2023
• Last Verified: Jan 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Synthekine: CART; CD19-CART; Chimeric antigen receptor; IL-2
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Cyclophosphamide; Fludarabine

Study Results

No Results Posted as of Jan 13, 2023