Overview
This is an open label Phase 1/2 study, the purpose of the trial is to assess the safety, tolerability, pharmacokinetics, and antitumor activity of ASKB589 in patients suffering from advanced or metastatic solid tumors. Patients with gastric cancer/gastroesophageal junction adenocarcinoma and pancreatic cancer are preferred.
Eligibility
Inclusion Criteria:
- According to RECIST 1.1 criteria, all patients must have at least one measurable lesion, and the tumor lesions must be accurately measured in at least one dimension, and lesions previously treated with radiotherapy or local therapy are only evaluated as non-target lesions. Bone metastatic lesions are not considered as measurable lesions;
- ECOG performance status (PS) 0-1;
- The results of the laboratory tests must meet all the following criteria:
（1）Haemoglobin≥9 g/dL；platelet count≥ 100 × 109/L；absolute neutrophil count≥ 1.5 × 109/L；
（2）Albumin≥ 3.0g/dL；total bilirubin ≤ 1.5 times the upper limit of normal (ULN)；aspartate
transaminase and alanine aminotransferase≤ 2.5 times ULN if no demonstrable liver
metastases ( ≤5 times ULN in the presence of liver metastases);
（3）Creatinine clearance≥ 50ml/min；
（4）Prothrombin time, international normalized ratio, and activated partial thromboplastin
time≤1.5×ULN (except for patients receiving anticoagulant therapy)
4.Life expectancy of at least 3 months;
5.Patients who are supposed to be enrolled into the monotherapy dose escalation study must
meet all the following criteria:
1. Patients of either gender, aged from 18 years old to 70;
2. Patients with histologically or cytologically confirmed diagnosis of advanced
unresectable or metastatic malignant solid tumor, for whom have no standard therapy or
have no access to standard therapy for various reasons.
6.Patients who are supposed to be enrolled into the monotherapy dose expansion study must
meet all the following criteria:
1. Patients of either gender, aged from 18 years old to 75；
2. Patients with histologically or cytologically confirmed diagnosis of advanced
unresectable or metastatic gastric cancer, gastroesophageal junction adenocarcinoma
and pancreatic cancer, for whom have no standard therapy or have no access to standard
therapy for various reasons, and that tumor tissue samples are CLDN18.2 positive
detected by central laboratory (medium-high expression)；
3. Other tumor types with good potential benefits will be included according to the
results of the clinical results of same target products (CLDN18.2-positive tumors).
7.Patients who are supposed to be enrolled into the dose escalation of ASKB589 combined
with chemotherapy should meet all the following criteria:
1. Patients of either gender, aged from 18 years old to 70.
2. Patients with gastric cancer, gastroesophageal junction adenocarcinoma and pancreatic
cancer who are tolerant to CAPOX, GEM+Nab-P chemotherapy.
3. Patients with gastric cancer, gastroesophageal junction adenocarcinoma who are
intolerant to anti-human epidermal growth factor receptor 2 (anti-HER2) drug therapy.
4. Other tumor types with good potential benefits will be included according to the
results of mono-therapy dose expansion and the clinical results of same target
products.
8.Patients who are supposed to be enrolled into the dose expansion of ASKB589 combined with
chemotherapy should meet all the following criteria:
1. Patients of either gender, aged from 18 years old to 75.
2. Patients with gastric cancer, gastroesophageal junction adenocarcinoma and pancreatic
cancer who are tolerant to CAPOX, GEM+Nab-P chemotherapy, and that tumor tissue
samples are CLDN18.2 positive detected by central laboratory (medium-high expression).
3. Patients with gastric cancer, gastroesophageal junction adenocarcinoma that who are
intolerant to anti-HER2 drug therapy.
4. Other tumor types with good potential benefits will be included according to the
results of this study and the clinical results of same target products.
Exclusion Criteria:
1. Patients have a history of severe allergic reactions to monoclonal antibodies or are
intolerance to monoclonal antibodies, or those who are allergic to experimental drug
and any component of the drug.
2. Patients have received a treatment of whole blood or blood component transfusion or
various growth factor treatments within 14 days prior to enrollment.
3. Patients have received anti-tumor therapy within 14 days prior to enrollment，including
but not limited to radiotherapy, chemotherapy, targeted therapy, treatment with herbal
medications or other treatments that have known antitumor activity . Patients who have
undergone palliative radiotherapy for bone metastases and whose acute toxicity has
returned to normal can be selected;
4. Patients have received systemic immunosuppressive therapy（such as systemic
corticosteroids）within 14 days prior to enrollment. However, patients using a
physiologic replacement dose of hydrocortisone or its equivalent (defined as up to
30mg per day of hydrocortisone or 10mg per day of prednisone) are allowed；patients are
allowed to receive a single dose of systemic corticosteroids treatment；
5. Patients have participated in other clinical trials within 28 days prior to
enrollment; patients who have participated monoclonal antibody clinical trials within
2 months prior to sign written informed consent form also cannot participate in this
trial；
6. Patients have received major surgical operation within 28 days prior to enrollment or
schedule to perform major surgery during the period of this clinical trial;
7. Patients have gastrointestinal diseases such as gastrinoma, duodenitis, gastric ulcer,
duodenal ulcer, pancreatitis or upper gastrointestinal hemorrhage, caused by
nonmalignant tumor (gastric cancer, gastroesophageal junction adenocarcinoma and
pancreatic cancer)；
8. Known to have irritable bowel syndrome, ulcerative colitis, Crohn's disease, gastric
outlet obstruction, etc., or any other causes that can cause long-term chronic
nausea,persistent repeated vomiting or diarrhea, and uncontrolled or severe
gastrointestinal bleeding;
9. Have a history of diagnosed neurological or mental disorders, including epilepsy or
dementia;
10. Patients with any other malignant tumors within the past 5 years, cured cervical
carcinoma in situ, basal cell, or squamous cell skin cancer are not included.
11. Known active central nervous system (CNS) metastasis or suspected cancerous
meningitis;
12. There are moderate to large amounts of abdominal and pleural fluid. However, a small
number of asymptomatic and pleural effusion patients who do not need treatment are
allowed to be included;
13. Patients currently suffering from diseases that affect intravenous injection and
venous blood sampling;
14. Patients suffering from major cardiovascular diseases, including:
（1）Congestive heart failure (defined as New York Heart Association Class III or IV),
myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery
bypass graft, cerebrovascular accident (CVA) or hypertensive crisis within 6 months before
the first drug treatment；
（2）History of clinically significant ventricular arrhythmia (such as sustained ventricular
tachycardia, ventricular fibrillation or torsade de pointes)；
（3）Patients have an abnormality in the 12-lead electrocardiogram (ECG) including a
Fridericia's corrected QT interval (QTcF) greater than 450 milliseconds (ms) (males) or
greater than 470 ms (females).
（4）History or family history of congenital long QT syndrome；
（5）Cardiac arrhythmias requiring anti-arrhythmic drug therapy (patients suffering from
atrial fibrillation >1 month before the first administration of drug can be selected
according to the condition of patients);
（6）Left ventricular ejection fraction <50%；
15.Pregnant or lactating women; or women of childbearing age who have a positive blood
pregnancy test during screening period; or women of childbearing age and their spouses who
are unwilling to take effective contraceptive measures during the period of this clinical
trial and within 6 months after the end of the clinical trial;
16.Patients who are not meet the inclusion criteria based on the judgment of investigator；
17.Patients included in dose-escalation and expansion study of combined chemotherapy should
also exclude:
1. Patients with gastric cancer, gastroesophageal junction adenocarcinoma who are
allergic, intolerant or contraindicated to any other components of capecitabine and
oxaliplatin.
2. Patients with pancreatic cancer who are allergic, intolerant or contraindicated any
components of gemcitabine and albumin bound paclitaxel for injection.