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

Small Cell Lung Cancer Extensive Stage Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05680922
• Other study ID #: LB2102-1001
• Status: Recruiting
• Phase: Phase 1
• Start date: July 26, 2023
• Est. completion date: March 2028

Study information

• Verified date: February 2024
• Source: Legend Biotech USA Inc
• Contact: Legend Biotech USA
• Phone: 17323175050
• Email: medical.information[@]legendbiotech.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 41
• Est. completion date: March 2028
• Est. primary completion date: January 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (ß-human chorionic gonadotropin [ß-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

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Large Cell Neuroendocrine Carcinoma of the Lung
• Lung Neoplasms
• Small Cell Lung Cancer Extensive Stage
• Small Cell Lung Carcinoma

Intervention

Biological:
• LB2102
DLL3 directed autologous Chimeric Antigen Receptor T-cells

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Kentucky - Markey Cancer Center	Lexington	Kentucky
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Legend Biotech USA Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To characterize the safety and tolerability of LB2102 and determine recommended dose for expansion (RDE)	Multiple doses will be tested to establish a recommended dose	28 days
Primary	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)	Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study	90 days
Secondary	To evaluate the preliminary efficacy of LB2102	Measured by Response Evaluation Criteria In Solid Tumors (RECIST)	Through study completion, a minimum of 2 years
Secondary	To characterize the pharmacokinetics of LB2102 in blood	CAR-positive T cell counts in cells/microliter (µL) blood	Through study completion, a minimum of 2 years
Secondary	To evaluate the immunogenicity of LB2102	Number of subjects with presence of anti-LB2102 antibodies	Through study completion, a minimum of 2 years