A LM-302 Combination With Other Anti-Tumor Therapies Phase ll Study

An Open-label, Multicenter Phase II Clinical Study to Evaluate the Efficacy, Safety, and Tolerability of the LM-302 Combination With Other Anti-tumor Treatment in Subjects With CLDN18.2-positive Advanced Gastro-Intestinal Cancer.

This study is to evaluate the efficacy of the LM-302 Combination With Other Therapies in patients with CLDN18.2-positive Advanced Digestive Tract Tumor.

Study Overview

• Status: Recruiting
• Conditions: Malignant Neoplasms of Digestive Organs
• Intervention / Treatment: Drug: LM-302; Drug: Toripalimab; Drug: Capecitabine; Drug: Tegafur, Gimeracil and Oteracil Potassium Capsules; Drug: Nivolumab; Drug: Apatinib; Drug: Gemcitabine

Detailed Description

Primary Objective:

To evaluate the efficacy of the LM-302 + Toripalimab regimen in subjects with CLDN18.2-positive advanced gastro-Intestinal cancer

Secondary Objectives:

To evaluate the correlation between CLDN18.2 and PD-L1 expression levels and the antitumor activity of the LM-302 + Toripalimab regimen.

• Study Type: Interventional
• Enrollment (Estimated): 276
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Paul Kong; Phone Number: 021-68889618; Email: paulkong@lanovamed.com
• Study Contact Backup: Name: Alex Yuan; Phone Number: 021-68889618; Email: AlexYuan@Lanovamed.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai East Hospital
    • Contact: Jin Li

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
2. Aged 18-80 years old (including boundary values) .
3. Eastern Cooperative Oncology Group (ECOG) performance status of0-1.
4. Life expectancy ≥ 3 months.
5. Subjects with advanced gastrointestinal tumors diagnosed histologically and/or cytologically and who have failed or are intolerant to prior standard first-line therapy (imaging confirmation required)
6. CLDN18.2-positive subjects.
7. At least one measurable lesion.
8. Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose.
9. Subjects who are able to communicate well with investigators and understand and adhere to the requirements of this study.

Exclusion Criteria:

1. Subjects with known HER2-positive gastric cancer/adenocarcinoma of the gastroesophageal junction
2. Subjects have participated in any other clinical trial within 28 days prior to 1st dosing of investigational medicinal product (IMP).
3. Subjects with anti-tumor treatment within 21 days prior to 1st dosing of IMP.
4. Previous immunotherapy and grade ≥3 irAE or grade ≥2 immune-related myocarditis. (for cohorts treated with combination PD-1).
5. Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
6. Present peripheral sensory or motor neuropathy ≥ grade 2.
7. Subjects with uncontrolled pain.
8. Subjects with symptomatic/active central nervous system(CNS)metastases.
9. Subject who have uncontrollable third space effusion.
10. Subjects with known hypersensitivity to antibody therapy.
11. Subjects have treated with the same target.
12. Subjects have received Strong inhibitor/strong inducer of CYP3A4 within 14 days prior to first dose.
13. Use of any live vaccines within 28 days prior to 1st dosing of IMP.
14. Subjects with current or previous interstitial lung diseases or pneumonia requiring oral or intravenous glucocorticoids for adjuvant therapy.
15. Subjects on anticoagulants, such as heparin and vitamin K antagonists.
16. Clinically uncontrollable persistent recurrent vomiting.
17. Uncontrollable/severe gastrointestinal bleeding, ulceration or diarrhea within 28 days prior to first dose of IMP.
18. Subjects who received major surgery or interventional treatment within28 days prior to the first dosing of IMP.
19. Subjects who have other cancers, other than the one treated in this trial, within 2 years prior to screening.
20. Subjects who have severe cardiovascular disease.
21. Subjects who have uncontrolled or severe illness.
22. Subjects who take systemic corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications within 2 weeks prior to the first dosing of IMP.
23. Subjects with a known history of autoimmune diseases.
24. Subjects who have a history of immunodeficiency disease.
25. Subjects with HIV infection, active HBV or HCV infection.
26. Child-bearing potential female who have positive results in pregnancy test within 7 days before the first dose or are lactating.
27. Subject who have a known psychiatric diseases or disorders that may affect compliance with the trial.
28. Subject who is judged as not eligible to participate in this study by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM-302 in combination with Toripalimab	Drug: LM-302; Q2W/Q3W，Administered intravenously; Drug: Toripalimab; Q2W/Q3W,Administered intravenously
Experimental: LM-302 in combination with other therapies	Drug: LM-302; Q2W/Q3W，Administered intravenously; Drug: Toripalimab; Q2W/Q3W,Administered intravenously; Drug: Capecitabine; BID,Oral Administration; Drug: Tegafur, Gimeracil and Oteracil Potassium Capsules; BID,Oral Administration; Drug: Nivolumab; Q4W,Administered intravenously; Drug: Apatinib; QD,Oral Administration; Drug: Gemcitabine; Q4W,Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression free survival according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	112 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate (ORR)	112 weeks
DOR	Duration of response (DOR)	112 weeks
DCR	Disease control rate (DCR = CR + PR + SD)	112 weeks
OS	Overall survival (OS)	112 weeks
AEs	Incidence of adverse events	112 weeks
SAEs	Incidence of serious adverse events	112 weeks
Temperatures	Temperatures	112 weeks
Pulse in BPM	Beat per Minute	112 weeks
Blood Pressure	Blood Pressure in mmHg	112 weeks
Weight	Weight in Kg	112 weeks
Height	Height in centimeter	112 weeks
Blood Routine examination	Laboratory tests-Blood Routine examination	112 weeks
Urine Routine test	Laboratory tests-Urine Routine test	112 weeks
Blood biochemistry	Laboratory tests-Blood biochemistry	112 weeks
Coagulation function	Laboratory tests- Coagulation function	112 weeks
LVEF	Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage	112 weeks
HR	12-lead electrocardiogram (ECG) in HR	112 weeks
RR	12-lead electrocardiogram (ECG) in RR	112 weeks
PR	12-lead electrocardiogram (ECG) in PR	112 weeks
QRS	12-lead electrocardiogram (ECG) in QRS	112 weeks
QT	12-lead electrocardiogram (ECG) in QT	112 weeks
QTcF	12-lead electrocardiogram (ECG) in QTcF	112 weeks
ECOG score	Eastern Cooperative Oncology Group score	112 weeks
PK Parameter:Cmax	Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)	112 weeks
PK Parameter：Tmax	PK Parameter:Time of Maximum Observed Concentration (Tmax)	112 weeks
PK Parameter: AUC	PK Parameter: Area Under the Concentration-time Curve(AUC)	112 weeks
PK Parameter: Cmax,ss	PK Parameter: Steady State Maximum Concentration(Cmax,ss)	112 weeks
PK Parameter: Cmin,ss	PK Parameter: Steady State Minimum Concentration(Cmin,ss)	112 weeks
PK Parameter: CLss	PK Parameter: Systemic Clearance at Steady State (CLss)	112 weeks
PK Parameter:Rac	PK Parameter: Accumulation Ratio (Rac)	112 weeks
PK Parameter: t1/2	PK Parameter: Elimination Half-life (t1/2)	112 weeks
PK Parameter: Vss	PK Parameter: Volume of Distribution at Steady-State (Vss)	112 weeks
PK Parameter: DF	PK Parameter: Degree of Fluctuation (DF)	112 weeks
Immunogenicity of LM-302	Anti-Drug antibody and Nab (if neccessary) will be tested.	112 weeks
Biomarker correlation	For the detection of CLDN18.2 and PD-L1	112 weeks
AE/SAE	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	112 weeks

Collaborators and Investigators

• Sponsor: LaNova Medicines Zhejiang Co., Ltd.
• Investigators: Principal Investigator: Jieer Ying, Zhejiang Cancer Hospital; Principal Investigator: Chunmei Bai, Peking Union Medical College Hospital; Principal Investigator: Hongming Pan, Sir run run shaw Hospital; Principal Investigator: Jin Li, Shanghai East Hospital; Principal Investigator: Haiping Jiang, Zhejiang University; Principal Investigator: Rushen Zhao, Zibo Municipal Hospital; Principal Investigator: Yiping Mou, Zhejiang Provincial People's Hospital; Principal Investigator: Haijiao Yan, The First People's Hospital of Changzhou; Principal Investigator: Aiping Zhou, Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Principal Investigator: Xianglin Yuan, Tongji Hospital; Principal Investigator: Mingzhu Huang, Fudan University; Principal Investigator: Jing Dai, Zhongnan Hospital; Principal Investigator: Yabin Xia, First Affiliated Hospital of Wannan Medical College; Principal Investigator: Lixin Wan, Nanyang Central Hospital; Principal Investigator: Jun Zhou, Shanghai Gaobo Cancer Hospital; Principal Investigator: Youwei Zhang, Xuzhou Central Hospital; Principal Investigator: Ning Wu, Shanghai Pudong New District Gongli Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 19, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 6, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Nivolumab; Gemcitabine; Tegafur; toripalimab; apatinib; gimeracil; potassium oxonate
• Other Study ID Numbers: LM302-02-201

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