Trial Title:
Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells in Subjects With Unresectable, Locally Advanced, or Metastatic Gastric, Gastroesophageal Junction (GEJ), Esophageal, or Pancreatic Adenocarcinoma
NCT ID:
NCT05539430
Condition:
Gastric Cancer
Gastroesophageal-junction Cancer
Esophageal Cancer
Pancreatic Cancer
Conditions: Official terms:
Adenocarcinoma
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:
LB1908
Description:
Claudin 18.2-Targeted autologous Chimeric Antigen Receptor T-cells
Arm group label:
Experimental LB1908
Summary:
This is a Phase 1, Open-Label, Dose Escalation and Expansion, Multicenter Study of
Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells in Subjects with Unresectable,
Locally Advanced, or Metastatic Gastric, Gastroesophageal Junction (GEJ), Esophageal, or
Pancreatic Adenocarcinoma
Detailed description:
This is a Phase 1, open label, multicenter study to evaluate Claudin 18.2-targeting CAR-T
cells (LB1908) in adult subjects with unresectable, locally advanced or metastatic
gastric, GEJ, esophageal, or pancreatic adenocarcinoma. Patients will be confirmed to
have sufficient expression of Claudin 18.2 as part of a prescreening. The study comprises
a dose-escalation component (Part A) and a dose-expansion component (Part B). In part A,
patients with gastric, GEJ, or esophageal adenocarcinoma will be treated with LB1908 at
protocol-defined dose level, with escalation to higher doses in subsequent patients
guided by evaluation of protocol-defined dose limiting toxicities (DLTs). Part A will
identify the recommended dose for expansion (RDE) to be tested in part B in two cohorts:
a gastric, GEJ and esophageal adenocarcinoma cohort as well as a pancreatic
adenocarcinoma cohort. Part B will aim to identify the recommended dose for phase 2
(RP2D).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Be willing and able to provide written informed consent
2. Be a female or male ≥ 18 and ≤ 75 years old at the time of signing of the informed
consent
3. For Part A and B: subjects with histologically/cytologically confirmed unresectable,
locally advanced or metastatic adenocarcinoma of the stomach, GEJ, or distal
esophagus for which standard treatment is considered intolerable, unlikely to confer
significant clinical benefit, is no longer effective, does not exist, or subject is
ineligible or declines standard therapy.
For Part B only: subjects with histologically/cytological confirmed unresectable,
locally advanced or metastatic adenocarcinoma of the pancreas for which standard
treatment is considered intolerable, unlikely to confer significant clinical
benefit, is no longer effective, does not exist, or subject is ineligible or
declines standard therapy.
4. Subjects must have received prior therapy as follows:
- For gastric, GEJ, or esophageal adenocarcinoma, previous treatment must have
included a fluoropyrimidine and/or platinum containing regimen. Subjects with
HER2-neu-positive (HER2+) disease must have also received prior anti-HER2+
therapy.
- For pancreatic adenocarcinoma, previous treatment must have included
fluoropyrimidine and/or gemcitabine containing regimen.
5. Presence of CLDN18.2 positive tumors with staining intensity of ≥ 1+ in ≥ 50% of
tumor cells by immunohistochemistry (performed by central laboratory during
Prescreening)
6. Presence of ≥ 1 radiologically measurable lesion per Response Evaluation Criteria In
Solid Tumors (RECIST) Version 1.1.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Life expectancy of at least 4 months per investigator judgment.
9. Have adequate organ function
10. Women of childbearing potential must have a negative pregnancy test at screening
11. All Subject must agree to practice a highly effective method of contraception from
the time of signing the ICF to 1 year after receiving a LB1908 infusion.
12. Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively,
until at least 1 year after receiving a LB1908 infusion.
Exclusion Criteria:
1. Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product.
2. Prior treatment with claudin 18.2-targeted therapy.
3. Antitumor therapy prior to apheresis during the protocol-defined window
4. Subjects who have a history of esophageal or gastric resection that the investigator
considers is at increased risk of bleeding or perforation;
5. Unstable/active ulcer, varices, or digestive tract bleeding or recent digestive
surgery that may have increased risk of bleeding;
6. Clinically significant ascites, pleural or peritoneal effusions requiring weekly
clinical intervention at screening.
7. Patients requiring anticoagulant therapy such as warfarin or heparin
8. Patients requiring long-term antiplatelet therapy
9. Primary immunodeficiency
10. Known brain metastasis or leptomeningeal metastasis.
11. Subjects with heavy tumor burden such as significant lung disease or extensive liver
metastases.
12. Active autoimmune disease receiving immunosuppressants (e.g., cyclosporine or high
dose systemic steroids) within 2 weeks or 5 half-lives prior to screening
13. Impaired cardiac function or clinically significant cardiac disease as defined by
the protocol
14. Previous or concurrent malignancy not meeting protocol-defined exceptions
15. 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:
16. Current known active infection with human immunodeficiency virus (HIV), hepatitis B,
and/or hepatitis C virus (HBV/HCV).
17. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to
LB1908 excipients, such as dimethyl sulfoxide; or to fludarabine, cyclophosphamide,
or tocilizumab.
18. Ongoing toxicity from previous anticancer therapy that has not resolved to Grade 2
or less, except for alopecia, fatigue, nausea, and constipation.
19. Major surgery within 4 weeks prior to apheresis, or planned within 4 weeks after
LB1908 administration.
20. Pregnant or breast-feeding.
21. Plans to become pregnant or breastfeed, or father a child within 1 year after
receiving a LB1908 infusion.
22. Previous history of allogeneic HSCT, organ transplant, or in preparation for organ
transplant.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Grace Bae
Phone:
313-576-8030
Email:
baeg@karmanos.org
Contact backup:
Last name:
Main Line
Phone:
800 527 6266
Facility:
Name:
Roswell Park Comprehensive Cancer Center
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sarah Chatley
Phone:
800-767-9355
Email:
askroswell@roswellpark.org
Contact backup:
Last name:
Online Form https://www.roswellpark.org/become-patient
Facility:
Name:
OHSU Knight Cancer Institute
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Contact:
Last name:
Richard Maziarz, MD
Phone:
503-494-1080
Email:
trials@ohsu.edu
Facility:
Name:
Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
FHCC Intake
Phone:
206-606-1024
Email:
hutchdoc@fredhutch.org
Start date:
April 18, 2023
Completion date:
December 2025
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/NCT05539430
