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
DRUGLM-302
Q2W/Q3W，Administered intravenously
DRUGToripalimab
Q2W/Q3W,Administered intravenously
DRUGCapecitabine
BID,Oral Administration
BID,Oral Administration
DRUGNivolumab
Q4W,Administered intravenously
DRUGApatinib
QD,Oral Administration
DRUGGemcitabine
Q4W,Administered intravenously
DRUGTislelizumab
Q2W Administered intravenously
DRUGAnlotinib
QD,Oral Administration
DRUGBenmelstobart
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. Participants 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. Participants 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. Participants must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose. 9. Participants who are able to communicate well with investigators and understand and adhere to the requirements of this study.
Exclusion criteria
1. Participants with known HER2-positive gastric cancer/adenocarcinoma of the gastroesophageal junction 2. Participants have participated in any other clinical trial within 28 days prior to 1st dosing of investigational medicinal product (IMP). 3. Participants 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. Participants with uncontrolled pain. 8. Participants with symptomatic/active central nervous system(CNS)metastases. 9. Participants who have uncontrollable third space effusion. 10. Participants with known hypersensitivity to antibody therapy. 11. Participants have treated with the same target. 12. Participants 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. Participants with current or previous interstitial lung diseases or pneumonia requiring oral or intravenous glucocorticoids for adjuvant therapy. 15. Participants 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. Participants who received major surgery or interventional treatment within28 days prior to the first dosing of IMP. 19. Participants who have other cancers, other than the one treated in this trial, within 2 years prior to screening. 20. Participants who have severe cardiovascular disease. 21. Participants who have uncontrolled or severe illness. 22. Participants 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. Participants with a known history of autoimmune diseases. 24. Participants who have a history of immunodeficiency disease. 25. Participants 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. Participants who have a known psychiatric diseases or disorders that may affect compliance with the trial. 28. Participants 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 |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
China
Contacts
CONTACTAlex Yuan
CONTACTPaul Kong
PRINCIPAL_INVESTIGATORJin Li
Shanghai East Hospital
PRINCIPAL_INVESTIGATORJieer Ying
Zhejiang Cancer Hospital
PRINCIPAL_INVESTIGATORHaiping Jiang
First Affiliated Hospital of Zhejiang University
PRINCIPAL_INVESTIGATORRushen Zhao
Zibo Municipal Hospital
PRINCIPAL_INVESTIGATORChunmei Bai
Peking Union Medical College Hospital
PRINCIPAL_INVESTIGATORYu Zheng
Sir Run Run Shaw Hospital
PRINCIPAL_INVESTIGATORJing Dai
Zhongnan Hospital
PRINCIPAL_INVESTIGATORYiping Mou
Zhejiang Provincial People's Hospital
PRINCIPAL_INVESTIGATORHaijiao Yan
The First People's Hospital of Changzhou
PRINCIPAL_INVESTIGATORAiping Zhou
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
PRINCIPAL_INVESTIGATORXianglin Yuan
Tongji Hospital
PRINCIPAL_INVESTIGATORYabin Xia
First Affiliated Hospital of Wannan Medical College
PRINCIPAL_INVESTIGATORMingzhu Huang
Fudan University
PRINCIPAL_INVESTIGATORLixin Wan
Nanyang Central Hospital
PRINCIPAL_INVESTIGATORJun Zhou
Shanghai Gaobo Cancer Hospital
PRINCIPAL_INVESTIGATORYouwei Zhang
Xuzhou Central Hospital
PRINCIPAL_INVESTIGATORNing Wu
Shanghai Pudong New District Gongli Hospital
PRINCIPAL_INVESTIGATORDeliang Fu
Huashan Hospital
PRINCIPAL_INVESTIGATORKuirong Jiang
The First Affiliated Hospital with Nanjing Medical University
PRINCIPAL_INVESTIGATORLiang Liu
Zhongshan Hospital Affiliated with Fudan University
PRINCIPAL_INVESTIGATORShiwei Guo
Changhai Hospital
PRINCIPAL_INVESTIGATORWenhai Huang
Jinshan Hospital Affiliated to Fudan University
Outcome results
None listed