search
Back to results

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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LB2102
Sponsored by
Legend Biotech USA Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer Extensive Stage

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Moffitt Cancer CenterRecruiting
  • University of Kentucky - Markey Cancer CenterRecruiting
  • Dana-Farber Cancer InstituteRecruiting
  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental LB2102

Arm Description

DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T)

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

To evaluate the preliminary efficacy of LB2102
Measured by Response Evaluation Criteria In Solid Tumors (RECIST)
To characterize the pharmacokinetics of LB2102 in blood
CAR-positive T cell counts in cells/microliter (μL) blood
To evaluate the immunogenicity of LB2102
Number of subjects with presence of anti-LB2102 antibodies

Full Information

First Posted
December 21, 2022
Last Updated
October 16, 2023
Sponsor
Legend Biotech USA Inc
search

1. Study Identification

Unique Protocol Identification Number
NCT05680922
Brief Title
DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell 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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 26, 2023 (Actual)
Primary Completion Date
January 2028 (Anticipated)
Study Completion Date
March 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Legend Biotech USA Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer Extensive Stage, Large Cell Neuroendocrine Carcinoma of the Lung

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental LB2102
Arm Type
Experimental
Arm Description
DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T)
Intervention Type
Biological
Intervention Name(s)
LB2102
Intervention Description
DLL3 directed autologous Chimeric Antigen Receptor T-cells
Primary Outcome Measure Information:
Title
To characterize the safety and tolerability of LB2102 and determine recommended dose for expansion (RDE)
Description
Multiple doses will be tested to establish a recommended dose
Time Frame
28 days
Title
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)
Description
Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study
Time Frame
90 days
Secondary Outcome Measure Information:
Title
To evaluate the preliminary efficacy of LB2102
Description
Measured by Response Evaluation Criteria In Solid Tumors (RECIST)
Time Frame
Through study completion, a minimum of 2 years
Title
To characterize the pharmacokinetics of LB2102 in blood
Description
CAR-positive T cell counts in cells/microliter (μL) blood
Time Frame
Through study completion, a minimum of 2 years
Title
To evaluate the immunogenicity of LB2102
Description
Number of subjects with presence of anti-LB2102 antibodies
Time Frame
Through study completion, a minimum of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Legend Biotech USA
Phone
17323175050
Email
medical.information@legendbiotech.com
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tina Swartzlander
Phone
813-745-5517
Email
Tina.Swartzlander@moffitt.org
First Name & Middle Initial & Last Name & Degree
Alberto Chiappori, MD
Facility Name
University of Kentucky - Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhonglin Hao, MD
First Name & Middle Initial & Last Name & Degree
Heather L Heath
Email
heather.flynn@uky.edu
First Name & Middle Initial & Last Name & Degree
Zhonglin Hao, MD
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hope Wei, BA
Phone
617-632-3486
Email
HopeY_Wei@DFCI.HARVARD.EDU
First Name & Middle Initial & Last Name & Degree
Jordan Weiss, BA
Phone
617-632-4582
Email
jacob_sands@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Jacob Sands, MD
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adam Schoenfeld, MD

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs