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

Exclusion Criteria30

• 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
• Known status of acquired or inherited immunodeficiency without the ability of medical control or normalization.
• Known leptomeningeal metastases
• Active or symptomatic brain metastasis. Subjects with treated brain metastasis are allowed provided definitive therapy was completed at least 2 weeks prior to enrollment with at least documented stable disease and the subject is off supraphysiologic doses of steroid for at least 7 days. Additional requirements are met per protocol.
• Active autoimmune disease receiving immunomodulatory treatments (e.g., cyclosporine or high dose systemic steroids) prior to screening as follows:
• Within 2 weeks or 5 half-lives, whichever is longer
• Those with steroid replacement at physiologic doses and inhaled steroids recently or currently are not excluded.
• Impaired cardiac function or clinically significant cardiac disease not controlled by medications including:
• Unstable angina or myocardial infraction within 6 months prior to apheresis.
• History of cardiomyopathy with left ventricular ejection fraction (LVEF)\<45% as assessed by ECHO and MUGA scan.
• 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, such as:
• Active, uncontrolled, viral bacterial or systemic fungal infections.
• Requirement if supplemental oxygen to maintain oxygen saturation.
• Clinical evidence of dementia or altered mental status.
• Medically uncontrolled condition or insufficient recovery from an acute event within 6 months of screening.
• 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.
• subjects with HIV must be controlled on effective antiretroviral therapy for at least four weeks and have HIV viral load of less than 400 copies/mL prior to enrollment.
• subjects with active HBV must be on suppressive antiviral therapy prior to enrollment in the study.
• For subject with history of HBV and with serologic evidence of a resolved prior infection, the risk of HBV reactivation must be considered, and the need for anti-HBV prophylaxis must be carefully assessed prior to enrollment in the study.
• Subjects with untreated HCV infection may be eligible if the HCV is stable, the subject is not at risk for hepatic decompensation and the investigational cancer treatment is not expected to exacerbate the HCV infection.
• 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 (HSCT), organ transplant.