ST-067 in Combination With CD19-Directed CAR T-Cell Therapy (Liso-cel) in Relapsed/Refractory Large B-Cell Lymphoma

NCT ID: NCT07098364

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-01

Study Completion Date

2043-10-04

Brief Summary

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This phase I/II trial tests the safety, side effects, and best dose/regimen of ST-067 in combination with CD19-directed chimeric antigen receptor (CAR) T-cell therapy (liso-cel) and how well it works in treating patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (recurrent) or LBCL that has not responded to previous treatment (refractory). ST-067 is an engineered variant of the human cytokine interleukin-18 that may help the immune system kill cancer cells. Lisocabtagene maraleucel (liso-cel) is an autologous CAR T-cell therapy prepared using the person's own immune system (a group of cells, tissues, and organs that protect the body from attack by bacteria, viruses, and cancer cells) to fight the cancer. Giving ST-067 in combination with liso-cel may better treat patients with relapsed/refractory LBCL.

Detailed Description

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OUTLINE: This is a phase I, dose-escalation study of ST-067 followed by a phase II study.

Patients undergo leukapheresis and lymphodepleting chemotherapy between days -5 to -3 prior to treatment and receive liso-cel intravenously (IV) on day 0. Patients then receive ST-067 subcutaneously (SC) weekly on days 14, 21, and 28 or days 10, 17, and 24. Patients may continue to receive maintenance ST-067 SC at day 35 once weekly. Treatment continues for up to 8 doses in the absence of disease progression or unacceptable toxicity. Patients undergo x-ray imaging, and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) and/or positron emission tomography (PET) as well as lumbar puncture for cerebral spinal fluid (CSF) collection and bone marrow aspiration and biopsy as clinically indicated during screening and follow-up. Patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months after CAR T-cell infusion, then will be followed per standard of care long-term follow-up until the patient dies, is lost to follow-up, or withdraws consent.

Conditions

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Recurrent Diffuse Large B-Cell Lymphoma Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Recurrent Grade 3b Follicular Lymphoma Recurrent High-Grade B-Cell Lymphoma Recurrent Indolent B-Cell Non-Hodgkin Lymphoma Recurrent Primary Mediastinal Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Refractory Grade 3b Follicular Lymphoma Refractory High-Grade B-Cell Lymphoma Refractory Indolent B-Cell Non-Hodgkin Lymphoma Refractory Primary Mediastinal Large B-Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (liso-cel, ST-067)

Patients undergo leukapheresis and lymphodepleting chemotherapy between days -5 to -3 prior to treatment and receive liso-cel IV on day 0. Patients then receive ST-067 SC weekly on days 14, 21, and 28 or days 10, 17, and 24. Patients may continue to receive maintenance ST-067 SC at day 35 once weekly. Treatment continues for up to 8 doses in the absence of disease progression or unacceptable toxicity. Patients undergo x-ray imaging, and ECHO or MUGA during screening. Patients also undergo CT and/or PET as well as lumbar puncture for CSF collection and bone marrow aspiration and biopsy as clinically indicated during screening and follow-up. Patients undergo blood sample collection throughout the study.

Group Type EXPERIMENTAL

X-Ray Imaging

Intervention Type PROCEDURE

Undergo x-ray

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and CSF sample collection

Vevoctadekin

Intervention Type BIOLOGICAL

Given SC

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Leukapheresis

Intervention Type PROCEDURE

Undergo leukapheresis

Lisocabtagene Maraleucel

Intervention Type BIOLOGICAL

Given IV

Lumbar Puncture

Intervention Type PROCEDURE

Undergo lumbar puncture

Lymphodepletion Therapy

Intervention Type PROCEDURE

Undergo lymphodepletion chemotherapy

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Interventions

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X-Ray Imaging

Undergo x-ray

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood and CSF sample collection

Intervention Type PROCEDURE

Vevoctadekin

Given SC

Intervention Type BIOLOGICAL

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Echocardiography Test

Undergo ECHO

Intervention Type PROCEDURE

Leukapheresis

Undergo leukapheresis

Intervention Type PROCEDURE

Lisocabtagene Maraleucel

Given IV

Intervention Type BIOLOGICAL

Lumbar Puncture

Undergo lumbar puncture

Intervention Type PROCEDURE

Lymphodepletion Therapy

Undergo lymphodepletion chemotherapy

Intervention Type PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET scan

Intervention Type PROCEDURE

Other Intervention Names

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ST-067 ST 067 ST067 Variant ST-067 Engineered IL-18 Variant ST-067 Engineered Interleukin-18 Variant ST-067 Biopsy of Bone Marrow Biopsy, Bone Marrow CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography EC Echocardiography Leukocyte Adsorptive Apheresis Leukocytopheresis Therapeutic Leukopheresis White Blood Cell Reduction Apheresis Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes JCAR017 Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes JCAR017 Autologous Anti-CD19-EGFRt-4-1BB-zeta-modified CAR CD8+ and CD4+ T-lymphocytes JCAR017 Breyanzi JCAR 017 JCAR-017 JCAR017 Liso-cel LP Spinal Tap Lymphodepleting Therapy Lymphodepletion Blood Pool Scan Equilibrium Radionuclide Angiography Gated Blood Pool Imaging Gated Heart Pool Scan MUGA MUGA Scan Multi-Gated Acquisition Scan Radionuclide Ventriculogram Scan Radionuclide Ventriculography RNV Scan RNVG SYMA Scanning Synchronized Multigated Acquisition Scanning Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Conventional X-Ray Diagnostic Radiology Medical Imaging, X-Ray Plain film radiographs Radiographic Imaging Radiographic imaging procedure (procedure) Radiography RG Static X-Ray X-Ray Biological Sample Collection

Eligibility Criteria

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Inclusion Criteria

* Male or female \>= 18 years of age at the time of consent
* Patients with LBCL (including diffuse large B-cell lymphoma \[DLBCL\] not otherwise specified \[including DLBCL arising from indolent lymphoma\], high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B) with at least 2 lines of systemic therapy and an Food and Drug Administration (FDA)-approved indication for treatment with liso-cel
* Fluorodeoxyglucose (FDG)-avid disease on PET imaging before lymphodepletion or pathology evidence of active disease
* Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology
* Karnofsky performance status \>= 60%
* Adequate bone marrow function for lymphodepletion chemotherapy defined as: absolute neutrophil count (ANC) \>= 1000 cells/mm\^3, platelets \>= 50,000 cells/mm\^3, and hemoglobin \>= 8 g/dL, unless the cytopenias are due to bone marrow involvement by lymphoma in the opinion of the principal investigator (PI)
* Calculated creatinine clearance (Cockcroft/Gault) \> 30 mL/min/1.73 m\^2
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN) (or \< 5 x ULN for subjects with lymphomatous infiltration of the liver) and total bilirubin =\< 2 (or \< 3.0 for subjects with Gilbert's syndrome, lymphomatous infiltration of the liver, or hemolysis)
* Adequate pulmonary function based on pulmonary function testing (PFT), defined as forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) ratio of \>= 60% of predicted value and diffusing capacity of the lung for carbon monoxide (DLCO; corrected) \>= 40% of predicted value
* Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \>= 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA)
* Women of reproductive potential (defined as all women physiologically capable of becoming pregnant) must agree to use suitable methods of contraception for at least 30 days after the last dose of study therapy (ST-067)
* Males who have partners of reproductive potential must agree to use an effective barrier contraceptive method for at least 90 days after the last dose of study therapy (ST-067)
* Ability to understand and provide informed consent
* Able and willing to comply with study visit schedule and procedures, including tumor biopsy where feasible and with acceptable risk

Exclusion Criteria

* Planned use of out-of-specification liso-cel product
* History of another malignancy. The following are exceptions to this criterion:

* Adequately treated basal cell or squamous cell carcinoma of the skin.
* In situ prostate, ductal breast carcinoma breast, and cervical carcinoma.
* Adequately treated papillary, noninvasive bladder cancer.
* Other adequately treated stage 1 or 2 cancers currently in complete remission.
* Any other cancer that has been in remission for \>= 2 years
* Planned use of therapeutic doses of corticosteroids (\> 20 mg/day prednisone or equivalent) or other systemic immunosuppression within 7 days prior to leukapheresis or within 72 hours prior to liso-cel infusion. Topical and/or inhaled steroids are permitted
* Prior treatment with any CD19 CAR T-cell therapy
* For allogeneic hematopoietic cell transplant recipients, active graft versus host disease (GVHD) and/or systemic GVHD therapy within 30 days prior to planned leukapheresis
* Known active hepatitis B (detectable hepatitis B deoxyribonucleic acid \[DNA\]) or hepatitis C (detectable hepatitis C ribonucleic acid \[RNA\])
* Known human immunodeficiency virus (HIV) infection
* Pregnant or breastfeeding women
* Prior treatment with any IL-1 or IL-18 agonist and/or biosimilar agents, or an investigational agent within 4 weeks or 5 half-lives, whichever is shorter, prior to start of lymphodepletion
* Active autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\], celiac disease, or other serious chronic gastrointestinal conditions associated with diarrhea, autoimmune vasculitis, systemic lupus erythematosus, Wegener syndrome \[granulomatosis with polyangiitis\], myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) requiring immunosuppressive therapy. The following are exceptions to this criterion:

* Vitiligo.
* Alopecia.
* Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
* Type 1 diabetes mellitus.
* Psoriasis not requiring systemic treatment.
* Conditions considered to be low risk of serious deterioration by the PI
* History of any one of the following cardiovascular conditions within the past 6 months, unless clearance by a cardiologist is obtained: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, or unstable angina. History of other clinically significant cardiac disease that, in the opinion of the PI or designee, is a contraindication to study treatment is also excluded
* Significant electrocardiogram (ECG) abnormalities, including unstable cardiac arrhythmia requiring medication, second-degree atrioventricular (AV) block type II, third-degree AV block, \>= grade 2 bradycardia, or QT interval corrected using Fridericia's formula \> 500 ms irrespective of gender
* History or presence of clinically relevant central nervous system (CNS) pathology, such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis that in the opinion of the PI is a contraindication to study treatment.

* Patients with active parenchymal CNS involvement by malignancy will be excluded. Patients with prior or current secondary leptomeningeal CNS disease are eligible. CNS disease prophylaxis must be stopped at least 1 week prior to liso-cel infusion
* History of solid organ transplantation
* Active, serious, and uncontrolled infection(s)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Simcha Therapeutics

UNKNOWN

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexandre V. Hirayama, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Immunotherapy Intake Coordinator

Role: CONTACT

Phone: 206-606-4668

Email: [email protected]

Facility Contacts

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Immunotherapy Intake Coordinator

Role: primary

Other Identifiers

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NCI-2025-04890

Identifier Type: REGISTRY

Identifier Source: secondary_id

20817

Identifier Type: OTHER

Identifier Source: secondary_id

RG1125654

Identifier Type: -

Identifier Source: org_study_id