ST-067 in Combination With CD19-Directed CAR T-Cell Therapy (Liso-cel) in Relapsed/Refractory Large B-Cell Lymphoma
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)
3 other identifiers
interventional
33
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2025
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 25, 2025
CompletedFirst Posted
Study publicly available on registry
August 1, 2025
CompletedStudy Start
First participant enrolled
December 27, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 4, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 4, 2043
January 14, 2026
January 1, 2026
4.8 years
July 25, 2025
January 13, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Incidence of adverse events (AEs)
Will be graded in severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which will be graded according to the American Society for Transplantation and Cellular Therapy consensus criteria. The type, frequency, and severity of AEs and laboratory abnormalities will be listed and summarized.
Up to 4 years
Dose limiting toxicities (DLT)
Will be graded in severity according to the NCI CTCAE version 5.0. Will be summarized based on the DLT evaluable population. Final DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm. The target toxicity rate is 30%.
Up to 21 days following the first vevoctadekin (ST-067) dose
Optimal biological regimen
Will be assessed based on safety and tolerability, confirmation of maximum target engagement, optimal biological effects without undesirable clinical effects, pharmacokinetics parameters, and biological response data.
Up to 4 years
Complete response (CR) rate
Will be assessed by Lugano criteria. Will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence interval (CI) based on the efficacy-evaluable population.
At 3 months after liso-cel infusion
Secondary Outcomes (5)
CR rates
At 6 months after liso-cel infusion
Overall response rates
At 6 months after liso-cel infusion
Duration of response (DOR)
Up to 4 years
Progression free survival (PFS)
Up to 4 years
Overall survival (OS)
Up to 4 years
Study Arms (1)
Treatment (liso-cel, ST-067)
EXPERIMENTALPatients 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.
Interventions
Given SC
Undergo bone marrow biopsy
Undergo CT
Undergo ECHO
Undergo leukapheresis
Given IV
Undergo lumbar puncture
Undergo lymphodepletion chemotherapy
Undergo MUGA
Undergo x-ray
Undergo blood and CSF sample collection
Undergo PET scan
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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:
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- Simcha Therapeuticscollaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alexandre V. Hirayama, MD
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 25, 2025
First Posted
August 1, 2025
Study Start
December 27, 2025
Primary Completion (Estimated)
October 4, 2030
Study Completion (Estimated)
October 4, 2043
Last Updated
January 14, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share