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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Given SC
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CT
Undergo ECHO
Undergo leukapheresis
Given IV
Undergo lumbar puncture
Undergo lymphodepletion chemotherapy
Undergo MUGA
Undergo PET scan
Undergo x-ray
Undergo blood and CSF sample collection
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGIncidence 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.
Time frame: 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%.
Time frame: 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.
Time frame: 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.
Time frame: At 3 months after liso-cel infusion
CR rates
Will be assessed by Lugano criteria. Will be summarized along with the 2-sided 95% exact Clopper-Pearson CI based on the efficacy evaluable population.
Time frame: At 6 months after liso-cel infusion
Overall response rates
Will be assessed by Lugano criteria. Will be summarized along with the 2-sided 95% exact Clopper-Pearson CI based on the efficacy evaluable population.
Time frame: At 6 months after liso-cel infusion
Duration of response (DOR)
DOR will be assessed among responders. If a patient does not have an event for the DOR analyses, the patient will be censored at the date of the last adequate disease assessments or prior to the earliest censoring event. The censoring reason can include last contact/follow-up, discontinuation or completion of the study, receipt of another anticancer treatment with the exception of consolidation therapy with hematopoietic cell transplantation (HCT), and at least two consecutive missed scheduled disease assessments. Kaplan-Meier (KM) method will be used.
Time frame: Up to 4 years
Progression free survival (PFS)
If a patient does not have an event for the PFS analyses, the patient will be censored at the date of the last adequate disease assessments or prior to the earliest censoring event. The censoring reason can include last contact/follow-up, discontinuation or completion of the study, receipt of another anticancer treatment with the exception of consolidation therapy with HCT, and at least two consecutive missed scheduled disease assessments. KM method will be used.
Time frame: Up to 4 years
Overall survival (OS)
Analyses of OS will be performed in the safety population. For assessment of OS, data from surviving patients will be censored at the last time that the patient is known to be alive. KM method will be used.
Time frame: Up to 4 years
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