Clinical Trial 22196

• Overview

  Study Title:

  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

  Summary:

  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.

  Objective:

  Primary Objectives: Part A: To characterize the safety and Tolerability of LB2101 and determine recommended dose for expansion (RDE) Part B: To further characterize the safety and tolerability of LB2121 with the RDE identified in the dose-escalation and determined the recommended Phase 2 dose (RP2D) Secondary Objectives (Parts A and B): -To evaluate the preliminary efficacy of LB2102 -To characterize the pharmacokinetics of LB2102 in blood -To evaluate the immunogenicity of LB2102 Exploratory Objectives (Parts A and B): -To evaluate the additional preliminary efficacy of LB2102 -To characterize the distribution of LB2102 in target tissues and effusions (e.g. pleural fluid) -To evaluate DLL3 expression levels in target tissues and effusions (ascitic fluid and pleural fluid) over time -To explore the relationship between product related factors and pharmacokinetics, pharmacodynamics, safety, and efficacy -To explore whether there are predictive biomarkers of safety, response, resistance or relapse to LB2102

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  LB2102 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• 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 > Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a LB2102 infusion
  • Other criteria may apply

• 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
  • 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 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

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