gastric cancer/gastroesophageal junction adenocarcinoma with MET overexpression and/or amplification
Conditions
Interventions
Factorial group:Glumetinib
Phase one: dose expansion phase:Glumetinib+HB1801
Experimental Group:Glumetinib+HB1801
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Able to understand and voluntarily sign a written informed consent form (ICF); 2. Age> = 18 years old, gender is not limited; 3. Patients with advanced solid tumors confirmed by pathology or cytology; Among them, gastric cancer/gastroesophageal junction adenocarcinoma is required as follows: locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with or after at least first-line systemic standard therapy (defined as: locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with or after fluorouracil-containing combined with platinum/taxane chemotherapy with or without immunotherapy) after receiving at least first-line systemic therapy, and clear evidence of imaging disease progression during or after the last systemic therapy; Note: Disease progression occurs during or within 6 months after the end of postoperative adjuvant therapy, which can be regarded as a failure of front-line therapy; 4. Patients with unknown Her-2 expression should be confirmed before enrollment, and those with positive Her-2 expression should be treated with anti-Her-2 drugs in previous treatment; 5. MET overexpression and/or amplification in tumor tissue specimens/blood samples confirmed by the central laboratory (one of which is satisfied): (1). FISH: GCN>=5 and/or MET/CEP7 ratio >=2 (2). Immune conflict (IHC): 3+, >=50% (3). Immunohistochemistry: > = 2+, > = 50% and 3+, =3 months; 9. The function of major organs and bone marrow within 7 days before the first dose of study drug, in a non-intervention state, meet the following criteria: System & laboratory test value: blood routine (no blood transfusion, EPO, G-CSF, GM-CSF, TPO, etc. correction within 7 days before the first dose); Absolute neutrophil count (ANC) >=1.5×10^9/L ; Platelets>=100×10^9/L; hemoglobin >=90 g/L or >=5.6 mmol/L; Renal function: serum creatinine <=1.5× upper limit of normal range (ULN); Liver function: total bilirubin <=1.5×ULN (with liver metastases<=3×ULN); AST (aspartate aminotransferase) and ALT (alanine aminotransferase) <=2.5×ULN (with liver metastases<=5×ULN); Coagulation: International normalized ratio (INR) and prothrombin time (PT) <=1.5×ULN; Partially activated thromboplastin time (APTT) <=1.5×ULN;
Exclusion criteria
Exclusion criteria: 1. Participants who have used docetaxel in prior treatment; 2. Prior treatment with targeted MET drugs; 3. Patients with meningeal metastases, spinal cord compression, symptomatic or progressive brain metastases cannot be enrolled. Patients who have completed treatment (radiotherapy or surgery) for brain metastases and have stable metastases and no related symptoms (without drug control) within 4 weeks before the first dose can be enrolled; 4. Known hypersensitivity or intolerability to any component of the study protocol drug or its excipients; 5. Adverse events caused by prior anti-tumor therapy that did not recover to =II; 2). Left ventricular ejection fraction (LVEF) 470msec; or presence of risk factors for torsade de pointes, such as clinically significant hypokalemia judged by the investigator, family history of long QT syndrome, or history of familial arrhythmias (e.g., pre-excitation syndrome); 4). Previous or current severe and uncontrolled clinically significant cardiac arrhythmia; 5). Acute myocardial infarction, severe or unstable angina, congestive heart failure, aortic dissection, coronary or peripheral artery bypass grafting, cerebrovascular accident, transient ischemic attack or other grade 3 or above cardiovascular and cerebrovascular events; 6). Hypertension that cannot be effectively controlled (defined as systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg after treatment with standardized antihypertensive drugs); 7). Previous or current cardiomyopathy, which is judged by the investigator to have an impact on this trial; (2). Other clinically significant diseases: 1). Presence of >=grade 2 edema and lymphoid tissue edema that cannot be relieved by clinical intervention; 2). Severe infection within 4 weeks before the first use of the trial drug, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc.; Active infection requiring systemic antibiotics within 2 weeks prior to the first dose of trial dru
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recommended Phase 2 Dose;Dose Limited Toxicity;Objective Response Rate;Occurrence and incidence of adverse event/serious adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate;Occurrence and incidence of adverse event/serious adverse event;Overall Survival;Duration of Response?;MET expression and amplification level, tumor related gene variation;Progression-Free-Survival;Plasma concentrations of glumetinib and total docetaxel (albumin-bound) were determined;Objective Response Rate; | — |
Countries
China
Contacts
Public ContactXiangdong Cheng
Zhejiang Cancer Hospital
Outcome results
None listed