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

Phase 2

Recruiting

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

• Registration Number: NCT05934331
• Lead Sponsor: LaNova Medicines Zhejiang Co., Ltd.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-06-19
• Study First Submitted QC: 2023-06-28
• Study First Posted: 2023-07-06
• Study Start: 2023-07-27
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-06
• Last Update Posted: 2025-09-12
• Primary Completion: 2026-07-01
• Study Completion: 2028-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 276

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LM-302 in combination with Toripalimab	LM-302	-
LM-302 in combination with Toripalimab	Toripalimab	-
LM-302 in combination with other therapies	LM-302	-
LM-302 in combination with other therapies	Toripalimab	-
LM-302 in combination with other therapies	Capecitabine	-
LM-302 in combination with other therapies	Tegafur, Gimeracil and Oteracil Potassium Capsules	-
LM-302 in combination with other therapies	Nivolumab	-
LM-302 in combination with other therapies	Apatinib	-
LM-302 in combination with other therapies	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
PFS	112 weeks	Progression free survival according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Shanghai East Hospital; 🇨🇳 Shanghai, China