A 1/2 Phase Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ASKB589 in Patients With Locally Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- ASKB589 Injection
- Conditions
- Malignant Solid Tumor
- Sponsor
- Jiangsu Aosaikang Pharmaceutical Co., Ltd.
- Enrollment
- 199
- Locations
- 2
- Primary Endpoint
- Number of participants with serious adverse events (SAE) as assessed by CTCAE v5.0
- Status
- Active, Not Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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:
- •Patients of either gender, aged from 18 years old to 70;
Exclusion Criteria
- •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.
- •Patients have received a treatment of whole blood or blood component transfusion or various growth factor treatments within 14 days prior to enrollment.
- •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;
- •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；
- •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；
- •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;
- •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)withinwithin 3 months prior to enrollment；Patients have gastric inlet and outlet obstruction or suspected obstruction within 1 months prior to enrollment；
- •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;
- •Have a history of diagnosed neurological or mental disorders, including epilepsy or dementia;
- •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;
Arms & Interventions
ASKB589 Injection
Experimental: ASKB589 Injection ASKB589 Injection treatment. This phase 1/II trial will include two stages, a dose escalation stage and an expansion stage.
Intervention: ASKB589 Injection
Outcomes
Primary Outcomes
Number of participants with serious adverse events (SAE) as assessed by CTCAE v5.0
Time Frame: up to 21 days following last dose
An SAE is defined as any untoward medical occurrence that, at any dose: a.) Results in death; b.) Is life-threatening; c.) Requires inpatient hospitalization or prolongation of existing hospitalization; d.) Results in persistent or significant disability/incapacity; e.) Is a congenital anomaly/birth defect; f.) Other important medical events; The number of participants who experience an SAE will be presented.
The incidence and case number of DLT (Dose Limiting Toxicity) during observation period
Time Frame: up to 21 or 28 days following first dose
DLT is short for Dose Limiting Toxicity，dose-limiting describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.
Number of participants with adverse events as assessed by CTCAE v5.0
Time Frame: up to 21 days following last dose
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented.
Maximum Tolerated Dose (MTD）
Time Frame: up to 21 or 28 days following first dose
The MTD was defined as the highest dose of ASKB589 not causing DLT in more than 33% of patients in the first treatment cycle.
The recommended dose
Time Frame: from date of treatment start until data cut-off, up to 2 years
The recommended dose will be determined during the dose escalation and dose expansion stage of the study.
Objective response rate
Time Frame: from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years
Evaluation of objective response rate assessed by response evaluation criteria in solid tumors version 1.1(RECIST 1.1)
Secondary Outcomes
- Pharmacokinetics:terminal elimination half life (T1/2)(Up to 21 days after injection)
- Pharmacokinetics:apparent volume of distribution (Vz/F)(Up to 21 days after injection)
- Pharmacokinetics:Area Under Curve (AUC)(Up to 21 days after injection)
- Pharmacokinetics: Mean ResidenceTime（MRT）(Up to 21 days after injection)
- Pharmacokinetics: plasma clearance rate (CL)(Up to 21 days after injection)
- Pharmacokinetics: steady-state peak concentration (Css_max)(Up to 21 days after injection)
- Pharmacokinetics: time to steady-state peak concentration (Tss_max)(Up to 21 days after injection)
- Pharmacokinetics: minimum value of steady plasma drug concentration（Css_min）(Up to 21 days after injection)
- Evaluation of immunogenicity(from date of treatment start until data cut-off, up to 2 years)
- Pharmacokinetics:maximum Plasma Concentration [Cmax](Up to 21 days after injection)
- Pharmacokinetics:time to maximum observed plasma concentration (Tmax)(Up to 21 days after injection)
- Pharmacokinetics:elimination rate constant（Kel）(Up to 21 days after injection)
- Objective response rate（ORR）(from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years)
- disease control rate（DCR）(from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years)
- Duration of Response（DOR）(from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years)
- Progression free survival（PFS）(from date of treatment start until the date of disease progression or until death due to any causes, up to 2 years.)
- Overall survival（OS）(from the date of treatment start until the documented date of death from any cause，up to 2 years.)