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

NCT05539430 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: LB1908-1001
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 9

Brief 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

Conditions

Gastric Cancer; Esophageal Cancer; Gastroesophageal-junction Cancer; Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• To characterize the safety and tolerability of LB1908 and determine the optimal dose or recommended dose for expansion (RDE)

  Multiple doses will be tested to establish a recommended dose.

  28 days

• To further characterize the safety and tolerability of LB1908 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 Outcomes (3)

• To evaluate the preliminary efficacy of LB1908

  Through study completion, a minimum of 2 years

• To characterize the pharmacokinetics of LB1908 in blood

  Through study completion, a minimum of 2 years

• To evaluate the immunogenicity of LB1908

  Through study completion, a minimum of 2 years

Study Arms (1)

Experimental LB1908

EXPERIMENTAL

Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells

Biological: LB1908

Interventions

LB1908 BIOLOGICAL

Claudin 18.2-Targeted autologous Chimeric Antigen Receptor T-cells

Experimental LB1908

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent.
• Be a female or male ≥ 18 and ≤ 75 years old at the time of signing of the prescreening ICF.
• For Part A and Part B Cohort MR1 only:
• Subjects with histologically/cytologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the GC/GEJC/EC for which standard treatment is considered intolerable, unlikely to confer significant clinical benefit, is no longer effective, or subject is ineligible or declines standard therapy.
• Subjects must have received prior therapy as follows:
• 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.
• Neoadjuvant/adjuvant treatment will be considered as a prior regimen if disease progression occurred during treatment or within 6 months of cessation of treatment.
• For Part B Cohort MR2 only:
• Subjects with histologically/cytologically confirmed unresectable, locally advanced or metastatic PDAC for which standard treatment is considered intolerable, unlikely to confer significant clinical benefit, is no longer effective, or subject is ineligible or declines standard therapy.
• Subjects must have received prior therapy as follows:
• Previous treatment must have included fluoropyrimidine and/or gemcitabine containing regimen.
• Neoadjuvant/adjuvant treatment will be considered as a prior regimen if disease progression occurred during treatment or within 6 months of cessation of treatment.
• For Part B Cohort CR1 only:
• Subjects with histologically/cytologically confirmed metastatic GC/GEJC/EC with RECIST v1.1 SD or PR at the initial response evaluation during first-line SOC treatment.
• Subjects with locally advanced, unresectable disease for whom radiation is not planned may be eligible with Sponsor approval.

You may not qualify if:

• Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product.
• Antitumor therapy prior to Screening as follows (Part A and Part B Monotherapy Regimen \[second- or later-line subjects\] subjects only):
• Any systemic anticancer therapy (including investigational) within 7 days or at least 5 halflives, whichever is shorter.
• Monoclonal antibody therapy within 2 weeks. Type of monoclonal antibody should be communicated with Sponsor.
• Unstable/active ulcer, varices, or digestive tract bleeding or recent digestive surgery that may have increased risk of bleeding.
• Clinically significant ascites, pleural or peritoneal effusions requiring weekly clinical intervention at screening.
• Subjects who are on therapeutic anticoagulation. (Note: subjects who are on therapeutic antiplatelet therapy or prophylactic anticoagulation are permitted to participate if deemed to not be at an increased risk of bleeding from their underlying disease or procedures and are required to obtain approval from Sponsor. Similarly, subjects who can have therapeutic anticoagulation de-escalated to prophylactic dosing prior to LB1908 infusion are also eligible).
• Known inherited or acquired immune deficiency without the ability of medical control or normalization.
• History or known brain metastasis or leptomeningeal metastasis. Part B Cohorts MR1 and MR2: Subjects can have brain metastases if previously treated and confirmed stable for at least 4 weeks prior to study entry.
• Subjects with heavy tumor burden such as significant lung disease or extensive liver metastases (e.g., \> 5 liver lesions or a single dominant lesion \> 5 cm in maximal dimension).
• Active autoimmune disease receiving immunosuppressants (e.g., cyclosporine or high dose systemic steroids) prior to screening as follows:
• Within 2 weeks or 5 half-lives, whichever is longer (those with inhaled or topical steroids recently or currently are not excluded.)
• Immune-related AEs due to prior immune checkpoint therapy must be ≤ Grade 1 with no ongoing immunosuppression, including a systemic steroid dose ≤ 20 mg daily of prednisone equivalent.
• Impaired cardiac function or clinically significant cardiac disease including:
• Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to apheresis.

Sponsors & Collaborators

• Legend Biotech USA Inc: lead

Study Sites (9)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

John Theurer Cancer Center at HackensackUMC

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2022
• First Posted: September 14, 2022
• Study Start: April 18, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)