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

NCT05707676 | Terminated Phase 1

• 1 other identifier: LB4330-CHN-I-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Solid Tumor

Keywords

LB4330

Outcome Measures

Primary Outcomes (3)

• MTD/RP2D

  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.

  up to study completion,approximately 24 months

• DLT occurrence and frequency (dose escalation phase)

  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).

  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)

• AE, SAE occurrence and frequency (according to NCI CTCAE 5.0)

  According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

  up to 90 days following last dose

Secondary Outcomes (9)

• Serum PK parameters

  Up to finished treatment

• Pharmacodynamic index

  through study completion, an average of 8 months.

• Immunogenicity

  up to 90 days following last dose

• Overall response rate (ORR)

  through study completion, an average of 8 months.

• Disease control rate (DCR)

  through study completion, an average of 8 months.

Study Arms (2)

Dose Escalation

EXPERIMENTAL

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.

Drug: LB4330

Single Drug Expansion

EXPERIMENTAL

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).

Drug: LB4330

Interventions

LB4330 DRUG

LB4330

Dose Escalation; Single Drug Expansion

Eligibility Criteria

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

You may qualify if:

• Subjects must meet all of the following criteria to be eligible for enrollment:
• \. Age between 18 and 75 years (inclusive), regardless of sex. 2.
• Dose-Escalation Phase: Histologically or cytologically confirmed advanced malignant solid tumors.
• Monotherapy Expansion Phase: Histologically or cytologically confirmed advanced gastric/gastroesophageal junction adenocarcinoma, pancreatic ductal adenocarcinoma, or other solid tumors that have failed standard treatment, or for which there is no standard treatment, or for whom standard treatment is currently unsuitable. 3.
• Dose-Escalation Phase: At least one evaluable lesion based on RECIST v1.1.
• Monotherapy Expansion Phase: At least one measurable lesion based on RECIST v1.1 (lesions previously treated with radiotherapy or localized therapy are not considered measurable unless they have clearly progressed or persisted for at least 3 months post-radiotherapy).
• Monotherapy Expansion Phase: Must provide a prior Claudin 18.2 test report; if unavailable, archived or fresh tumor tissue samples must be submitted.
• Cohorts A, B, C: Require Claudin 18.2 expression (≥1% of tumor cells with staining intensity of 1+ or above).
• Cohort D: Must be Claudin 18.2 negative.
• Cohort E: Must not have known Claudin 18.2 expression (≥1% of tumor cells with staining intensity of 1+ or above).
• \. ECOG performance status of 0-1. 6. Expected survival time of at least 3 months. 7. Adequate organ function:
• Hematologic (no transfusion or hematopoietic growth factors within 14 days prior):
• ANC ≥ 1.5 × 10⁹/L
• Platelets ≥ 100 × 10⁹/L
• Hemoglobin ≥ 90 g/L

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded:
• 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.
• Participation in another investigational drug or therapy trial within 4 weeks prior to first dose.
• Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to first dose, or scheduled elective surgery during the study.
• Prior treatment with IL-10-targeted agents.
• 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).
• Immunomodulatory agents (e.g., thymosin, IL-2, interferons) within 14 days prior to first dose.
• Live or attenuated vaccines within 4 weeks prior to first dose.
• Prior allogeneic stem cell or organ transplantation.
• Unresolved adverse events from prior anticancer therapy (excluding alopecia, Grade 2 peripheral neuropathy, or well-controlled hypothyroidism), unless ≤ Grade 1 per CTCAE v5.0.
• 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.
• Active infection requiring systemic treatment.
• 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.
• Known gastrointestinal disorders such as irritable bowel syndrome with symptoms (e.g., chronic nausea, vomiting, diarrhea) or gastric outlet obstruction.
• History of immunodeficiency, including HIV antibody positivity.

Sponsors & Collaborators

• L & L Bio Co., Ltd., Ningbo, China: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200120, China

Location

Study Officials

• Xianjun Yu, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

• Jian Zhang, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2022
• First Posted: February 1, 2023
• Study Start: November 30, 2022
• Primary Completion: December 20, 2024
• Study Completion: December 20, 2024
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

CN (1)