RECRUITING

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

Conditions

Small Cell Lung Cancer Extensive Stage Large Cell Neuroendocrine Carcinoma of the Lung

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood 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.

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

Quick Facts

Study Start:2023-07-26

Study Completion:2028-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05680922

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Legend Biotech USA

CONTACT

17323175050

medical.information@legendbiotech.com

Study Locations (Sites)

Moffitt Cancer Center

Tampa, Florida, 33612

United States

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10017

United States

Collaborators and Investigators

Sponsor: Legend Biotech USA Inc

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-26

Study Completion Date2028-03

Study Record Updates

Study Start Date2023-07-26

Study Completion Date2028-03

Terms related to this study

Additional Relevant MeSH Terms

Small Cell Lung Cancer Extensive Stage
Large Cell Neuroendocrine Carcinoma of the Lung