A Phase 1/2 Open-Label Study Evaluating the Safety and Efficacy of ST-067 in Combination With CD19-Directed CAR T-Cell Therapy in Patients With Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL)

Status: Recruiting
Location: See location...
Intervention Type: Procedure, Biological
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

Locations
United States
Washington
Fred Hutch/University of Washington Cancer Consortium
RECRUITING
Seattle
Contact Information
Primary
Immunotherapy Intake Coordinator
immunotherapy@fredhutch.org
206-606-4668
Time Frame
Start Date: 2025-11-01
Estimated Completion Date: 2043-10-04
Participants
Target number of participants: 33
Treatments
Experimental: 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.
Sponsors
Leads: Fred Hutchinson Cancer Center
Collaborators: Simcha Therapeutics

This content was sourced from clinicaltrials.gov

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