Trial Title:
DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer
NCT ID:
NCT05680922
Condition:
Small Cell Lung Cancer Extensive Stage
Large Cell Neuroendocrine Carcinoma of the Lung
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Neuroendocrine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
LB2102
Description:
DLL3 directed autologous Chimeric Antigen Receptor T-cells
Arm group label:
Experimental LB2102
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tina Swartzlander
Phone:
813-745-5517
Email:
Tina.Swartzlander@moffitt.org
Investigator:
Last name:
Alberto Chiappori, MD
Email:
Principal Investigator
Facility:
Name:
University of Kentucky - Markey Cancer Center
Address:
City:
Lexington
Zip:
40536
Country:
United States
Status:
Recruiting
Contact:
Last name:
Zhonglin Hao, MD
Contact backup:
Last name:
Heather L Heath
Email:
heather.flynn@uky.edu
Investigator:
Last name:
Zhonglin Hao, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hope Wei, BA
Phone:
617-632-3486
Email:
HopeY_Wei@DFCI.HARVARD.EDU
Contact backup:
Last name:
Jordan Weiss, BA
Phone:
617-632-4582
Email:
jacob_sands@dfci.harvard.edu
Investigator:
Last name:
Jacob Sands, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10017
Country:
United States
Status:
Recruiting
Contact:
Last name:
Adam Schoenfeld, MD
Phone:
646-608-4042
Email:
schoenfa@mskcc.org
Contact backup:
Last name:
Sophie Hieronymi
Email:
hierons@mskcc.org
Start date:
July 26, 2023
Completion date:
March 2028
Lead sponsor:
Agency:
Legend Biotech USA Inc
Agency class:
Industry
Source:
Legend Biotech USA Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05680922
