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

Phase 1

Terminated

• Conditions: Solid Tumor
• Interventions: Drug: LB4330

• Registration Number: NCT05707676
• Lead Sponsor: L & L Bio Co., Ltd., Ningbo, China

Brief 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.

Study Timeline

• Study Start: 2022-11-30
• Study First Submitted: 2022-12-28
• Study First Submitted QC: 2023-01-31
• Study First Posted: 2023-02-01
• Primary Completion: 2024-12-20
• Study Completion: 2024-12-20
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-04
• Last Update Posted: 2025-09-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded:

1. Received chemotherapy, biologic therapy, targeted therapy, or immunotherapy within 4 weeks prior to first dose; radiotherapy, endocrine therapy, or oral fluoropyrimidines within 2 weeks;traditional Chinese medicine with antitumor indications within 1 week;or nitrosoureas/mitomycin C within 6 weeks.

2. Participation in another investigational drug or therapy trial within 4 weeks prior to first dose.

3. Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to first dose, or scheduled elective surgery during the study.

4. Prior treatment with IL-10-targeted agents.

5. Systemic corticosteroids (prednisone >10 mg/day or equivalent) or immunosuppressants within 14 days prior to first dose, except for: topical, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids; short-term prophylactic steroids (e.g., to prevent contrast reactions).

6. Immunomodulatory agents (e.g., thymosin, IL-2, interferons) within 14 days prior to first dose.

7. Live or attenuated vaccines within 4 weeks prior to first dose.

8. Prior allogeneic stem cell or organ transplantation.

9. Unresolved adverse events from prior anticancer therapy (excluding alopecia, Grade 2 peripheral neuropathy, or well-controlled hypothyroidism), unless ≤ Grade 1 per CTCAE v5.0.

10. Meningeal metastases, spinal cord compression, or unstable brain metastases requiring steroids or anti-epileptic drugs within 4 weeks before enrollment. Stable brain metastases off steroids/anti-epileptics for ≥4 weeks are allowed.

11. Active infection requiring systemic treatment.

12. Tumor thrombus involving major blood vessels or adjacent organ invasion (e.g., stomach, aorta, trachea) posing high risk of bleeding/perforation, or existing bleeding/perforation/fistula.

13. Known gastrointestinal disorders such as irritable bowel syndrome with symptoms (e.g., chronic nausea, vomiting, diarrhea) or gastric outlet obstruction.

14. History of immunodeficiency, including HIV antibody positivity.

15. Active syphilis, active hepatitis B [HBsAg-positive and HBV DNA >200 IU/mL or above assay's lower limit of detection], or active hepatitis C (HCV antibody positive but HCV RNA below assay limit is allowed). Patients on non-interferon antiviral therapy are eligible.

16. Interstitial lung disease (excluding radiation-induced fibrosis not requiring steroids).

17. Serious cardiovascular or cerebrovascular conditions, including but not limited to:

    • Significant arrhythmia or conduction abnormalities (e.g., Grade II-III AV block requiring intervention)
    • QTcF >470 ms (female) or >450 ms (male)
    • Acute coronary syndrome, heart failure, aortic dissection,stroke, or other Grade ≥3 events within 6 months
    • NYHA class ≥II heart failure or LVEF <50%
    • Uncontrolled hypertension (resting BP ≥160/100 mmHg)

18. Active or recurrent autoimmune disease (e.g., SLE, RA, Crohn's, UC, vasculitis), except for: hypothyroidism requiring hormone replacement or stable type 1 diabetes on insulin.

19. Prior immune-related adverse event (irAE) of Grade ≥3 due to immunotherapy.

20. Clinically uncontrolled third-space or pericardial effusion requiring repeated drainage.

21. Grade ≥3 infusion-related reaction to previous biologic/protein therapy.

22. Known alcohol or substance abuse.

23. Psychiatric illness or poor compliance.

24. Pregnant or breastfeeding women.

25. History of other malignancies within the past 3 years, except for: non- melanoma skin cancer, biopsy-confirmed cervical carcinoma in situ, squamous intraepithelial lesion on Pap test, localized prostate cancer (Gleason <6), or completely resected in situ melanoma. Other low-risk or in-situ cancers may be allowed after sponsor consultation. 26. Other serious systemic diseases or conditions deemed unsuitable by the investigator.

27. Known HER2 positivity, MSI-H/dMMR, or mutations (e.g., KRAS) for which approved targeted therapies are available per guidelines.

28. Grade IV myelosuppression related to prior antitumor therapy. 29. Primary or secondary platelet count decreased or platelet-destructive diseases (e.g., Fanconi anemia, congenital platelet count decreased without megakaryocytes, May-Hegglin anomaly, aplastic anemia, bone marrow infiltration, radiation to bone marrow, megakaryocytic hypoplasia, ITP). 30. Arterial or venous thrombotic events within 6 months, including stroke (TIA, cerebral hemorrhage, infarction), DVT, or pulmonary embolism.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation	LB4330	Dose escalation uses an accelerated titration design combined with the standard 3+3 method.The planned maximum sample size for the dose-escalation phase is 39 subjects, with a maximum of 6 subjects per dose level.
Single Drug Expansion	LB4330	Planned cohorts and subject numbers:Cohort A: Advanced gastric and gastroesophageal junction adenocarcinoma with Claudin 18.2 expression that has failed standard treatment, with no more than three prior lines of therapy (up to 15 patients); Cohort B: Advanced pancreatic ductal adenocarcinoma with Claudin 18.2 expression that has failed standard treatment, with no more than three prior lines of therapy (up to 30 patients); Cohort C: Other advanced solid tumors with Claudin 18.2 expression that have failed standard treatment, with no more than three prior lines of therapy (a total of up to 15 patients); Cohort D: Advanced solid tumors without Claudin 18.2 expression (limited to ovarian cancer, cholangiocarcinoma, pancreatic cancer, gastric and gastroesophageal junction cancer) that have failed treatment, with no more than three prior lines of therapy (a total of up to 20 patients).

Primary Outcome Measures

Name	Time	Method
MTD/RP2D	up to study completion,approximately 24 months	MTD is determined based on the occurrence of DLTs. In this study, MTD is defined as the dose level at which 0/3 or 1/6 subjects experience a DLT, and at the next higher dose level, at least 2/3 or 2/6 subjects experience a DLT.
DLT occurrence and frequency (dose escalation phase)	The first period of LB4330 treatment (28 days for the first subject in the first dose group, 21 days for the rest subjects. If the administration is delayed, the DLT evaluation period should be extended to 7 days after the third administration)	The DLT evaluation period is the first cycle of LB4330 treatment (28 days for the first subject in the first dose cohort, and 21 days for all other subjects. If a dosing delay occurs, the DLT evaluation period should be extended accordingly to 7 days after the third administration).
AE, SAE occurrence and frequency (according to NCI CTCAE 5.0)	up to 90 days following last dose	According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

Secondary Outcome Measures

Name	Time	Method
Serum PK parameters	Up to finished treatment	AUC0-t and so on.
Pharmacodynamic index	through study completion, an average of 8 months.	Pharmacodynamic index: percentage of monocytes
Immunogenicity	up to 90 days following last dose	Immunogenicity index: positive rate, titer and duration of ADA; neutralizing antibody (NAb) analysis will be conducted if necessary.
Overall response rate (ORR)	through study completion, an average of 8 months.	Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST).
Disease control rate (DCR)	through study completion, an average of 8 months.	Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST).
Progression-free survival (PFS)	through study completion, an average of 8 months.	Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST).
Duration of response (DOR)	through study completion, an average of 8 months.	Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST).
OS	through study completion，an average of 1 year	Total survival period (OS): It is defined as the time from the start of using the study drug to the death due to any reason.
Biomarker	through study completion, an average of 8 months.	Biomarker: relationship between Claudin 18.2 expression level in tumor tissue and clinical response

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai Municipality, China