The phase 1 study is evaluating the combination of a CD19-targeting chimeric antigen receptor and an orthogonal IL-2 in patients with CD19-positive hematologic malignancies.
Trial Name: 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
ClinicalTrials.gov Identifier: NCT05665062
Sponsor: Synthekine
Recruitment Contact: Clinical Operations, 650.271.9888, clinicaltrialinfo@synthekine.com
Completion Date: November 2026
The first patient has been dosed in a phase 1 trial evaluating the combination of STK-009 and SYNCAR-001 in adult patients with relapsed or refractory CD19-positive hematologic malignancies.1
The 2-component therapy is made up of SYNCAR-001, a CD19-targeting chimeric antigen receptor (CAR) T-cell therapy, and STK-009, an engineered pegylated IL-2 cytokine. Preclinical studies have shown that treatment with STK-009 led to systemic and intratumoral expansion and activation of SYNCAR-001 cells. Even with substantially reduced cell doses, the combination of SYNCAR-001 and STK-009 reached complete responses in large lymphoma tumors.
A first-in-human, open-label, multicenter, phase 1 trial is now evaluating SYNCAR-001 plus STK-009 in patients with CD19-positive hematologic malignancies (NCT05665062).2
“While CAR T-cell therapies have had a major impact for patients with CD19+ hematologic malignancies, only a subset of these patients have durable benefit,” said Naiyer Rizvi, MD, chief medical officer of Synthekine, in a press release.1 “We believe that controllable, selective and sustained cytokine support is central to the advancement of this class of treatment, and STK-009 plus SYNCAR-001 has the potential to drive deeper and more durable responses while avoiding serious toxicities related to uncontrolled CAR T-cell expansion for patients in need of better treatment options.”
In the study, investigators will follow a 3+3 dose-escalation design followed by a dose-expansion phase which will evaluate the recommended phase 2 dose (RP2D).2 In the dose-escalation portion of the study, a single fixed dose of autologous SYNCAR-001 will be administered intravenously (IV) in combination with repeated sequential ascending doses of STK-009 subcutaneously (SC). The dose-expansion portion of the study will give patients a single fixed dose of autologous SYNCAR-001 via IV infusion in combination with repeated doses of STK-009 SC at the RP2D.
Patients aged 18 years and older with histologically confirmed relapsed/refractory hematologic malignancies, including chronic lymphocytic lymphoma and selected non-Hodgkin's lymphoma will be included in the study if they have had prior or current documentation of CD19 expression or high likelihood of CD19 expression based on disease histology and show no signs of central nervous system (CNS) disease or detectable evidence of CNS or meningeal disease on magnetic resonance imaging at the time of screening.
Those who have received prior CD19-directed therapy, including CD19 CAR T cells, prior allogeneic hematopoietic stem cell transplant within 6 months of enrollment, prior autologous hematopoietic stem cell transplant within 6 weeks of enrollment, or who have the presence of graft-versus-host disease will be excluded from the study.
The primary end points of the study are to evaluate dose-limiting toxicities and adverse events. Secondary end points include overall response rate, duration of response, progression-free survival, and pharmacokinetics.
Patients are actively being recruited for the study in California, Ohio, and New York, and the trial has an estimated completion date of November 2026.
“SYNCAR-001 plus STK-009 is our second clinical stage program at Synthekine and represents another key milestone in our journey to develop novel cytokine therapeutics for patients with refractory cancers,” said Debanjan Ray, chief executive officer of Synthekine, in the press release.2 “Our orthogonal IL-2 system is a unique platform that breaks new ground in the field of cell therapy. Combining STK-009 with SYNCAR-001 has the potential to overcome key limitations associated with current CD19 CAR T-cell therapies, such as poor expansion and limited persistence following T cell transfer. These limitations have been shown to correlate with poor response and relapse, particularly in challenging hematological malignancies. We look forward to further evaluating STK-009’s ability to offer a safer approach with improved efficacy and durability.”
