Malignant Neoplasms of Digestive Organs
Conditions
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.
Interventions
DRUGApatinib
QD,Oral Administration
DRUGGemcitabine
Q4W,Administered intravenously
DRUGLM-302
Q2W/Q3W，Administered intravenously
DRUGToripalimab
Q2W/Q3W,Administered intravenously
DRUGCapecitabine
BID,Oral Administration
BID,Oral Administration
DRUGNivolumab
Q4W,Administered intravenously
Sponsors
LaNova Medicines Zhejiang Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | 112 weeks | Progression free survival according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| ORR | 112 weeks | Objective response rate (ORR) |
| DOR | 112 weeks | Duration of response (DOR) |
| DCR | 112 weeks | Disease control rate (DCR = CR + PR + SD) |
| 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 |
| Blood Routine examination | 112 weeks | Laboratory tests-Blood Routine examination |
| Urine Routine test | 112 weeks | Laboratory tests-Urine Routine test |
| QRS | 112 weeks | 12-lead electrocardiogram (ECG) in QRS |
| 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 |
| QT | 112 weeks | 12-lead electrocardiogram (ECG) in QT |
| QTcF | 112 weeks | 12-lead electrocardiogram (ECG) in QTcF |
| 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: 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 |
| Blood biochemistry | 112 weeks | Laboratory tests-Blood biochemistry |
Countries
China
Contacts
Primary ContactAlex Yuan
Backup ContactPaul Kong
Outcome results
None listed