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

Inclusion Criteria:

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 informed consent

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.

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.
Presence of CLDN18.2 positive tumors with staining intensity of ≥ 1+ in ≥ 50% of tumor cells by immunohistochemistry (performed by central laboratory during Prescreening)
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 per investigator judgment.
Have adequate organ function
Women of childbearing potential must have a negative pregnancy test at screening
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.
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:

Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product.
Prior treatment with claudin 18.2-targeted therapy.
Antitumor therapy prior to apheresis during the protocol-defined window
Subjects who have a history of esophageal or gastric resection that the investigator considers is at increased risk of bleeding or perforation;
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.
Patients requiring anticoagulant therapy such as warfarin or heparin
Patients requiring long-term antiplatelet therapy
Primary immunodeficiency
Known brain metastasis or leptomeningeal metastasis.
Subjects with heavy tumor burden such as significant lung disease or extensive liver metastases.
Active autoimmune disease receiving immunosuppressants (e.g., cyclosporine or high dose systemic steroids) within 2 weeks or 5 half-lives prior to screening
Impaired cardiac function or clinically significant cardiac disease as defined by the protocol
Previous or concurrent malignancy not meeting protocol-defined 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:
Current known active infection with human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C virus (HBV/HCV).
Contraindications or life-threatening allergies, hypersensitivity, or intolerance to LB1908 excipients, such as dimethyl sulfoxide; or to fludarabine, cyclophosphamide, or tocilizumab.
Ongoing toxicity from previous anticancer therapy that has not resolved to Grade 2 or less, except for alopecia, fatigue, nausea, and constipation.
Major surgery within 4 weeks prior to apheresis, or planned within 4 weeks after LB1908 administration.
Pregnant or breast-feeding.
Plans to become pregnant or breastfeed, or father a child within 1 year after receiving a LB1908 infusion.
Previous history of allogeneic HSCT, organ transplant, or in preparation for organ transplant.