ACTIVE_NOT_RECRUITING

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 Gastroesophageal-junction Cancer Esophageal Cancer Pancreatic Cancer

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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, 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

Official Title

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

Quick Facts

Study Start:2023-04-18

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05539430

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 to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 prescreening ICF. 3. For Part A and Part B Cohort MR1 only: 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. Subjects with locally advanced, unresectable disease for whom radiation is not planned may be eligible with Sponsor approval. 7. Subjects who develop metachronous metastatic disease after prior (neo)adjuvant treatment for previously localized disease are eligible if at least 6 months have elapsed since completion of prior chemotherapy (and disease status is satisfied, as above). 8. Subjects must be clinically suitable to continue at least part of the initial first-line regimen during LB1908 manufacturing. 9. Negative for human epidermal growth factor receptor 2 (HER2) or ineligible to receive HER2-directed therapy. 10. Subjects must have received prior therapy as follows: * Acceptable SOC first-line regimens include (but are not limited to) leucovorin/fluorouracil/oxaliplatin (FOLFOX; modifications allowed) and capecitabine/oxaliplatin (CAPOX), with or without an approved immune checkpoint inhibitor. * Zolbetuximab is allowable as part of first-line SOC (subjects with prior zolbetuximab exposure require Sponsor approval prior to enrollment) 11. No investigational therapies in first-line therapy, unless the investigational product is discontinued prior to enrollment on this trial. 12. Subjects with metastatic PDAC with RECIST v1.1 SD or PR at the initial response evaluation during first-line SOC treatment. 13. Subjects with locally advanced, unresectable disease for whom radiation is not planned may be eligible with Sponsor approval. 14. Subjects who develop metachronous metastatic disease after prior (neo)adjuvant treatment for previously localized disease are eligible if at least 6 months have elapsed since completion of prior chemotherapy (and disease status is satisfied, as above). 15. Subjects must be clinically suitable to continue at least part of the initial first-line regimen during LB1908 manufacturing. 16. Subjects must have received prior therapy as follows: * Acceptable SOC first-line regimens include (but are not limited to) leucovorin/fluorouracil/irinotecan/oxaliplatin (FOLFIRINOX), nabpaclitaxel/ gemcitabine, and liposomal irinotecan/fluorouracil/leucovorin/oxaliplatin (NALIRIFOX). * Prior investigational therapies are exclusionary. 17. No investigational therapies in first-line therapy, unless the investigational product is discontinued prior to enrollment on this trial. 4. Presence of CLDN18.2 positive tumors with staining intensity of ≥ 1+ in ≥ 50% of tumor cells by immunohistochemistry (IHC) (Performed during Prescreening). * Subject has available formalin-fixed, paraffin-embedded (FFPE) 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. * If a subject had prior CLDN18.2 targeted therapy, subject may be required to have a formalin-fixed, paraffin-embedded tumor specimen in a tissue block or unstained serial slides accompanied by an associated pathology report that was obtained after exposure to CLDN18.2 targeted therapy, prior to enrollment, and fulfill criteria as outlined (\>50% expression) as directed by Sponsor. 5. Presence of ≥ 1 radiologically measurable lesion per RECIST v1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Life expectancy of at least 4 months per Investigator judgment.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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 prescreening ICF.
3. For Part A and Part B Cohort MR1 only:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Subjects with locally advanced, unresectable disease for whom radiation is not planned may be eligible with Sponsor approval.
7. Subjects who develop metachronous metastatic disease after prior (neo)adjuvant treatment for previously localized disease are eligible if at least 6 months have elapsed since completion of prior chemotherapy (and disease status is satisfied, as above).
8. Subjects must be clinically suitable to continue at least part of the initial first-line regimen during LB1908 manufacturing.
9. Negative for human epidermal growth factor receptor 2 (HER2) or ineligible to receive HER2-directed therapy.
10. Subjects must have received prior therapy as follows:
* Acceptable SOC first-line regimens include (but are not limited to) leucovorin/fluorouracil/oxaliplatin (FOLFOX; modifications allowed) and capecitabine/oxaliplatin (CAPOX), with or without an approved immune checkpoint inhibitor.
* Zolbetuximab is allowable as part of first-line SOC (subjects with prior zolbetuximab exposure require Sponsor approval prior to enrollment)
11. No investigational therapies in first-line therapy, unless the investigational product is discontinued prior to enrollment on this trial.
12. Subjects with metastatic PDAC with RECIST v1.1 SD or PR at the initial response evaluation during first-line SOC treatment.
13. Subjects with locally advanced, unresectable disease for whom radiation is not planned may be eligible with Sponsor approval.
14. Subjects who develop metachronous metastatic disease after prior (neo)adjuvant treatment for previously localized disease are eligible if at least 6 months have elapsed since completion of prior chemotherapy (and disease status is satisfied, as above).
15. Subjects must be clinically suitable to continue at least part of the initial first-line regimen during LB1908 manufacturing.
16. Subjects must have received prior therapy as follows:
* Acceptable SOC first-line regimens include (but are not limited to) leucovorin/fluorouracil/irinotecan/oxaliplatin (FOLFIRINOX), nabpaclitaxel/ gemcitabine, and liposomal irinotecan/fluorouracil/leucovorin/oxaliplatin (NALIRIFOX).
* Prior investigational therapies are exclusionary.
17. No investigational therapies in first-line therapy, unless the investigational product is discontinued prior to enrollment on this trial.
4. Presence of CLDN18.2 positive tumors with staining intensity of ≥ 1+ in ≥ 50% of tumor cells by immunohistochemistry (IHC) (Performed during Prescreening).
* Subject has available formalin-fixed, paraffin-embedded (FFPE) 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.
* If a subject had prior CLDN18.2 targeted therapy, subject may be required to have a formalin-fixed, paraffin-embedded tumor specimen in a tissue block or unstained serial slides accompanied by an associated pathology report that was obtained after exposure to CLDN18.2 targeted therapy, prior to enrollment, and fulfill criteria as outlined (\>50% expression) as directed by Sponsor.
5. Presence of ≥ 1 radiologically measurable lesion per RECIST v1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Life expectancy of at least 4 months per Investigator judgment.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Locations (Sites)

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

John Theurer Cancer Center at HackensackUMC

Hackensack, New Jersey, 07601

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263

United States

Duke University

Durham, North Carolina, 27705

United States

OHSU Knight Cancer Institute

Portland, Oregon, 97239

United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232

United States

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

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 Date2023-04-18

Study Completion Date2027-12

Study Record Updates

Study Start Date2023-04-18

Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

Gastric Cancer
Gastroesophageal-junction Cancer
Esophageal Cancer
Pancreatic Cancer