The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05680922
Recruitment Status : Recruiting
First Posted : January 11, 2023
Last Update Posted : February 9, 2024
Sponsor:
Information provided by (Responsible Party):
Legend Biotech USA Inc

Tracking Information
First Submitted Date  ICMJE December 21, 2022
First Posted Date  ICMJE January 11, 2023
Last Update Posted Date February 9, 2024
Actual Study Start Date  ICMJE July 26, 2023
Estimated Primary Completion Date January 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2023)
  • To characterize the safety and tolerability of LB2102 and determine recommended dose for expansion (RDE) [ Time Frame: 28 days ]
    Multiple doses will be tested to establish a recommended dose
  • 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) [ Time Frame: 90 days ]
    Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2023)
  • To evaluate the preliminary efficacy of LB2102 [ Time Frame: Through study completion, a minimum of 2 years ]
    Measured by Response Evaluation Criteria In Solid Tumors (RECIST)
  • To characterize the pharmacokinetics of LB2102 in blood [ Time Frame: Through study completion, a minimum of 2 years ]
    CAR-positive T cell counts in cells/microliter (μL) blood
  • To evaluate the immunogenicity of LB2102 [ Time Frame: Through study completion, a minimum of 2 years ]
    Number of subjects with presence of anti-LB2102 antibodies
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer
Official Title  ICMJE 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
Brief 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Small Cell Lung Cancer Extensive Stage
  • Large Cell Neuroendocrine Carcinoma of the Lung
Intervention  ICMJE Biological: LB2102
DLL3 directed autologous Chimeric Antigen Receptor T-cells
Study Arms  ICMJE Experimental: Experimental LB2102
DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T)
Intervention: Biological: LB2102
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 10, 2023)		 41
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2028
Estimated Primary Completion Date January 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Legend Biotech USA 17323175050 medical.information@legendbiotech.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05680922
Other Study ID Numbers  ICMJE LB2102-1001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Legend Biotech USA Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Legend Biotech USA Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Legend Biotech USA Inc
Verification Date February 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP