DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer.

Detailed Description
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This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer. The study comprises a dose-escalation component (Part A) and a cohort expansion component (Part B). Up to 41 subjects will be treated in this study. Part A will enroll and treat up to 24 subjects and Part B will be conducted after the recommended dose for expansion (RDE) has been identified in Part A and enroll up to 17 subjects. Both parts of this trial will include a Screening Period, a Pretreatment Period, a Treatment Period, a Follow-Up Period, and a Post-Progression Follow-Up Period.

Official Title
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A First in Human Dose Escalation and Cohort Expansion Study of DLL3-directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer Extensive Stage, Large Cell Neuroendocrine Carcinoma of the Lung

Intervention / Treatment
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* Biological: LB2102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be at least 18 years of age and willing and able to provide a written informed consent Have histologically/cytologically confirmed unresectable small cell lung carcinoma (SCLC), large cell neuroendocrine lung carcinoma (LCNEC), combined SCLC, or combined LCNEC as per WHO 2021 criteria Subjects who have at least one prior line of standard treatment, and have progressed after or have had an insufficient response, and for whom standard treatment is intolerable, unlikely to confer significant clinical benefit, is no longer effective, or the subject declines further standard treatment Have available formalin-fixed, paraffin-embedded tumor specimen in a tissue block or unstained serial slides accompanied by an associated pathology report prior to enrollment. Archival or fresh biopsy tissue is required Presence of ≥ 1 radiologically measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy of at least 4 months Have adequate organ function Women of childbearing potential must have a negative pregnancy test at screening using a highly sensitive serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) All subjects must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) from the time of signing the informed consent form (ICF) to 1 year after receiving a LB2102 infusion Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a LB2102 infusion Must have adequate leukapheresis material of non-mobilized cells available for manufacturing Exclusion Criteria: Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product Prior treatment with DLL3-targeted therapy Prior history of checkpoint inhibitor associated pneumonitis Clinically significant ascites, pleural or peritoneal effusions Primary acquired or inherited immunodeficiency syndromes Known leptomeningeal metastases Active or symptomatic brain metastasis. Subjects with treated brain metastasis are eligible provided additional requirements are met per protocol. Active autoimmune disease receiving immunomodulatory treatments (e.g., cyclosporine or high dose systemic steroids) Impaired cardiac function or clinically significant cardiac disease not controlled by medications Previous or concurrent malignancy, excluding certain exceptions Serious and /or uncontrolled medical condition that, in the Investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol Subjects with known active infection with HIV, hepatitis B, and/or hepatitis C virus (HBV/HCV) are not eligible unless additional protocol requirements are met. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to LB2102 excipients, such as dimethyl sulfoxide; or to fludarabine, cyclophosphamide, or tocilizumab Ongoing toxicity of organ functions from previous anticancer therapy that has not resolved to Grade 1 or less, except for alopecia Major surgery within 4 weeks prior to apheresis, or planned within 4 weeks after LB2102 administration Pregnant or breast-feeding Plans to become pregnant or breastfeed, or father a child within 1 year after receiving a LB2102 infusion Previous history of allogeneic hematopoietic stem cell transplantation (HSCT), organ transplant, or in preparation for organ transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental LB2102<br>DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T) | Biological: LB2102<br>* DLL3 directed autologous Chimeric Antigen Receptor T-cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the safety and tolerability of LB2102 and determine recommended dose for expansion (RDE) | Multiple doses will be tested to establish a recommended dose | 28 days | 
| To further characterize the safety and tolerability of LB2102 with the RDE identified in the dose-escalation and determine the recommended Phase 2 dose (RP2D) | Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the preliminary efficacy of LB2102 | Measured by Response Evaluation Criteria In Solid Tumors (RECIST) | Through study completion, a minimum of 2 years | 
| To characterize the pharmacokinetics of LB2102 in blood | CAR-positive T cell counts in cells/microliter (μL) blood | Through study completion, a minimum of 2 years | 
| To evaluate the immunogenicity of LB2102 | Number of subjects with presence of anti-LB2102 antibodies | Through study completion, a minimum of 2 years |