LM-302 for the Treatment of Subjects With Claudin18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma.

A Phase III, Open-Label, Multi Center, Randomized Study of LM-302 Versus Treatment of Physician's Choice (TPC) in Patients With CLDN18.2-Positive, Locally Advanced or Metastatic Gastric(GC) and Gastroesophageal Junction(GEJ) Adenocarcinoma.

This study will assess the efficacy and safety of LM-302 Versus Treatment of Physician's Choice (TPC) in Subjects With locally advanced or metastatic, Claudin (CLDN) 18.2-positive, Gastric or Gastroesophageal Junction Adenocarcinoma who have progressed on or after 2 lines of systemic therapy

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic GC and GCJ Adenocarcinoma
• Intervention / Treatment: Drug: LM-302; Drug: Apatinib; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 387
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Peking Union Medical College Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Shanghai East Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-80 years old, male and female
• Has histopathologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the gastric/gastroesophageal junction (G/GEJ AC).
• Has received and progressed on at least 2 lines of systemic therapy. A prior (neo)adjuvant systemic therapy that ended within 6 months prior to disease relapse is defined as the first line therapy.
• Centrally confirmed CLDN18.2-positive
• HER2 negative
• At least one measurable lesion according to the solid tumor response Evaluation Criteria (RECIST 1.1)
• ECOG: 0-1
• Expected survival ≥12 weeks;
• Good blood reserve and liver, kidney and coagulation function
• Willing to provide informed consent for study participation.

Exclusion Criteria:

• Within the first 5 years of randomization, there is a history of malignant tumors other than GC/GEJ adenocarcinoma, except for skin basal cell carcinoma, cervical carcinoma in situ, breast carcinoma in situ, and skin squamous cell carcinoma that have been cured and cured after treatment
• Individuals with a history of previous immunodeficiency, including those with other acquired or congenital immunodeficiency diseases, or those with a history of organ transplantation, allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation
• Urine protein qualitative result ≥ 3+, or urine protein qualitative result is 2+and 24-hour urine protein quantification>1g
• Individuals with a history of severe cardiovascular and cerebrovascular diseases
• Individuals who are unable to control or have serious illnesses, including but not limited to active infections requiring systemic antibiotic treatment within 2 weeks prior to initial medication, interstitial pneumonia/lung disease requiring intervention during screening, and tumor related pain requiring local treatment during screening
• Current peripheral sensory or motor neuropathy ≥ grade 2
• Uncontrollable third space effusion in clinical practice
• Received or planned to undergo major surgery or intervention during the study period within the first 28 days of randomization
• The researcher determined that there are other situations that are not suitable for participation in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM-302; Patients will accept LM-302 monotherapy	Drug: LM-302; LM-302 intravenous-injection every 2 weeks on Day 1 of each 14-day cycle
Active Comparator: Physician's choice Apatinib or Irinotecan; Patients will accept Apatinib or Irinotecan monotherapy	Drug: Apatinib; The subjects will receive Apatinib orally,qd; Drug: Irinotecan; The subjects will receive Irinotecan intravenous-injection,every 2 weeks on Day 1 of each 14-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined defined as the time from date of randomization until death from any cause.	up to 42 months
Progression Free Survival (PFS)	PFS was defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on Investigator assessment	up to 42 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	defined as the proportion of participants who achieve a best response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Investigator.	From start of treatment to date of documented disease progression, up to approximately 42 months
Duration of response (DoR)	defined time from the initial response (CR or PR) until documented tumor progression or death from any cause and based on Investigator assessment.	Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 42 months
Disease control rate (DCR)	defined as the proportion of participants who achieved CR, PR, or stable disease (SD) for a minimum of 6 weeks during study treatment, based on Investigator assessment.	From start of treatment to date of documented disease progression, up to approximately 42 months
AE and SAE	Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0	From signing the ICF until 28 days after EOT or accept other anti-cancer therapy,up to 40 days after last study dose
Evaluate the immunogenicity of LM-302	Anti-drug antibody (ADA) will be detected, the titer of ADA will be evaluated using the validated assay.	up to 42 months
Evaluation of pharmacokinetic characteristics of LM-302	Peak Plasma Concentration (Cmax) will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of LM-302	Area under the plasma concentration versus time curve (AUC) will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of LM-302	Trough concentration will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of total antibody	Peak Plasma Concentration (Cmax) will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of total antibody	Area under the plasma concentration versus time curve (AUC) will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of total antibody	Trough concentration will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of MMAE	Peak Plasma Concentration (Cmax) will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of MMAE	Area under the plasma concentration versus time curve (AUC) will be evaluated using PopPK model and simulation.	up to 42 months
Evaluation of pharmacokinetic characteristics of MMAE	Trough concentration will be evaluated using PopPK model and simulation.	up to 42 months

Collaborators and Investigators

• Sponsor: LaNova Medicines Zhejiang Co., Ltd.
• Investigators: Principal Investigator: Chunmei Bai, Peking Union Medical College Hospital; Principal Investigator: Jin Li, Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2024
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Heterocyclic Compounds; Camptothecin; Alkaloids; Irinotecan; apatinib
• Other Study ID Numbers: LM302-03-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No