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

ConditionsRecurrent Diffuse Large B-Cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent Grade 3b Follicular LymphomaRecurrent High-Grade B-Cell LymphomaRecurrent Indolent B-Cell Non-Hodgkin LymphomaRecurrent Primary Mediastinal Large B-Cell LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRefractory Grade 3b Follicular LymphomaRefractory High-Grade B-Cell LymphomaRefractory Indolent B-Cell Non-Hodgkin LymphomaRefractory Primary Mediastinal Large B-Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFred Hutchinson Cancer Center

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Planned use of out-of-specification liso-cel product

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Vevoctadekin

    Biological/Vaccine

    Given SC

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Leukapheresis

    Procedure/Surgery

    Undergo leukapheresis

  • Lisocabtagene Maraleucel

    Biological/Vaccine

    Given IV

  • Lumbar Puncture

    Procedure/Surgery

    Undergo lumbar puncture

  • Lymphodepletion Therapy

    Procedure/Surgery

    Undergo lymphodepletion chemotherapy

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET scan

  • X-Ray Imaging

    Procedure/Surgery

    Undergo x-ray

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood and CSF sample collection

Treatment groups

33 Participants
are divided into 1 treatment group
Group A: Treatment (liso-cel, ST-067)Experimental treatment 13 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 4 years
2

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
3

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
4

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fred Hutchinson Cancer Center

Lead sponsor

Simcha Therapeutics

Collaborator

Source ClinicalTrials.gov
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