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

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.

Inclusion Criteria:Be at least 18 years of age and willing and able to provide a written informed consentHave histologically/cytologically confirmed unresectable small cell lung carcinoma (SCLC), large cell neuroendocrine lung carcinoma (LCNEC), combined SCLC, or combined LCNEC as per WHO 2021 criteriaSubjects 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 treatmentHave 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 requiredPresence of ≥ 1 radiologically measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1Life expectancy of at least 4 monthsHave adequate organ functionWomen 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 infusionWomen and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a LB2102 infusionMust have adequate leukapheresis material of non-mobilized cells available for manufacturingExclusion Criteria:Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy productPrior treatment with DLL3-targeted therapyPrior history of checkpoint inhibitor associated pneumonitisClinically significant ascites, pleural or peritoneal effusionsPrimary acquired or inherited immunodeficiency syndromesKnown leptomeningeal metastasesActive 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 medicationsPrevious or concurrent malignancy, excluding certain exceptionsSerious 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 protocolSubjects 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 tocilizumabOngoing toxicity of organ functions from previous anticancer therapy that has not resolved to Grade 1 or less, except for alopeciaMajor surgery within 4 weeks prior to apheresis, or planned within 4 weeks after LB2102 administrationPregnant or breast-feedingPlans to become pregnant or breastfeed, or father a child within 1 year after receiving a LB2102 infusionPrevious history of allogeneic hematopoietic stem cell transplantation (HSCT), organ transplant, or in preparation for organ transplant