A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of LB4330 in Patients With Advanced Solid Tumors（MEETCD8-001）

Trial Title: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of LB4330 in Patients With Advanced Solid Tumors（MEETCD8-001）

NCT ID: NCT05707676

Condition: Solid Tumor

Conditions: Official terms:
Neoplasms

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: LB4330
Description: LB4330
Arm group label: Dose Escalation
Arm group label: Single Drug Expansion

Summary: This is a Phase I study designed to evaluate if LB4330, an anti-Claudin 18.2 and CD8 T cell activator fusion protein, is safe, tolerable and efficacious in participants with Advanced Solid Tumors

Detailed description: This first time in patients, open-label, multi-center study will have LB4330 administered intravenously (IV) in Patients with Advanced Solid Tumors. This study will have 2 parts: Part A which will have dose escalation cohorts and Part B which will have the dose expansion cohorts.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Age 18-80 (including boundary value) years old male or female. 2. Patients with advanced malignant solid tumor confirmed by histology or cytology (dose escalation stage), patients with advanced gastric and gastroesophageal junction adenocarcinoma, pancreatic duct adenocarcinoma or other solid tumors confirmed by histology or cytology (single drug expansion stage) who have failed standard treatment, or for whom standard treatment is not available or applicable at this stage. 3. (Dose escalation stage) At least one evaluable tumor lesion according to RECIST v1.1; (Single drug expansion stage) According to RECIST version 1.1, there is at least one measurable tumor lesion (tumor lesions located in the previous radiotherapy area or other local regional treatment areas are generally not regarded as measurable lesions, unless the lesions have a clear progression or persist three months after radiotherapy). 4. (Single drug expansion stage) Archived or fresh tumor tissue samples can be provided, and Claudin18.2 expression can be detected by IHC in the central laboratory (a clear cut off value will be defined according to the results of the dose increasing stage); Patients who cannot provide tumor tissue samples are also allowed to be included if they can provide previous test reports that meet the definition of Claudin 18.2 expression in the study. 5. ECOG performance score 0-1. 6. Expected survival time of more than 3 months. 7. Adequate organ function. 8. Eligible patients of childbearing potential (both men and women) must agree to use a reliable method of contraception (hormonal or barrier or abstinence, etc.) with their partners during the trial and for at least 90 days after the last dose; female patients of childbearing potential must have a negative blood or urine pregnancy test within 7 days prior to the first dose of study drug. 9. Patients must give informed consent to this study prior to the study and sign a written informed consent form voluntarily Exclusion Criteria: 1. Have received anti-tumor treatment such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy and immunotherapy within 4 weeks prior to the first dose of the study drug, except for the following: Herbal medicine with anti-tumor indications within 2 weeks prior to the first dose of study drug. Or received nitrosourea or mitomycin C within 6 weeks prior to the first dose of the study drug. 2. Have received other investigational agents or treatment within 4 weeks prior to the first dose of the study drug. 3. Have received major organ surgery (excluding needle biopsy) or have experienced significant trauma within 4 weeks prior to the first dose of study drug, or require elective surgery during the study period. 4. Have received systemic steroid therapy (prednisone >10 mg/day or equivalent) or other forms of immunosuppressive therapy within 14 days prior to the first dose of study drug; Except: topical, ocular, intra-articular, intranasal, and inhaled steroid therapy; and short-term corticosteroid prophylaxis (e.g., to prevent an allergic reaction to contrast material). 5. Have received allogeneic hematopoietic stem cell transplantation or organ transplantation. 6. The adverse reactions caused by previous anti-tumor treatment have not recovered to ≤ grade 1 per CTCAE 5.0 (except for toxicities without safety risk as judged by investigators, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.) 7. Patients with symptomatic parenchymal brain metastasis (BM) or leptomeningeal (LM) metastasis who are not suitable for treatment as judged by the investigator. 8. Patients with active infection which requires intravenous anti-infective therapy. 9. Patients with known lesions responsible for gastric bleeding or those considered by the investigator to have a greater risk for gastric bleeding. 10. irritable bowel syndrome with symptoms (such as chronic nausea, persistent repeated vomiting or diarrhea) and gastric outlet obstruction are known to exist. 11. Have a history of immunodeficiency, including HIV antibody test positive. 12. Active infection with hepatitis B (HBsAg-positive and HBV-DNA > 500 IU/ml or active infection with hepatitis C (patients with positive HCV antibody but HCV-RNA < lower limit of detection at the study site are allowed). (Note: enrollment of patients on prophylactic antiviral therapy other than interferon is permitted). 13. Patients with interstitial lung disease (excluding radiation-induced pulmonary fibrosis that does not require hormone treatment). 14. Known history of serious cardiovascular and cerebrovascular diseases, including but not limited to: Severe cardiac rhythm or conduction defects, such as arrhythmia requiring clinical intervention, second-degree to third-degree atrioventricular block, etc.; QT interval (QTcF) corrected by Fridericia method>470ms for female and> 450ms for male (see Appendix 8 for calculation formula);Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other ≥ grade 3 cardiovascular and cerebrovascular events within 6 months prior to the first dose of study drug; Symptomatic heart failure (New York Heart Association [NYHA] Functional Class II-IV) or left ventricular ejection fraction (LVEF) < 50%; Uncontrolled hypertension. 15. Patients with an active autoimmune disease or a documented history of autoimmune diseases with a risk of relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, ulcerative colitis, vasculitis, etc.), except for patients with clinically stable autoimmune thyroid disease or type I diabetes. 16. Have received immunotherapy and had ≥ grade 3 irAE. 17. Have experienced ≥ grade 3 infusion-related reactions to protein therapeutics. 18. Known history of other serious systemic diseases or other reasons that unsuitable for entry as determined by the investigator.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Fudan University Shanghai Cancer Center

Address:
City: Shanghai
Zip: 200120
Country: China

Status: Recruiting

Contact:
Last name: Xianjun Yu, Doctor
Email: yuxianjun@fudanpci.org

Contact backup:
Last name: Jian Zhang, Doctor
Email: syner2000@163.com

Start date: November 30, 2022

Completion date: September 2026

Lead sponsor:
Agency: L & L biopharma Co., Ltd., Shanghai China
Agency class: Industry

Source: L & L biopharma Co., Ltd., Shanghai China

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05707676