ASKB589 in Combination With CAPOX and Mentsimab in Patients With Locally Advanced or Metastatic Solid Tumors.
Study Details
Study Description
Brief Summary
This was an open-label, phase 1/2 study to evaluate safety, tolerability, pharmacokinetics, and antitumor activity of ASKB589 in combination with CAPOX and lindamycin in first-line treatment of patients with locally advanced, recurrent, or metastatic gastric and esophagogastric junction adenocarcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The study was a multicenter,open-label trial with 2 phases of dose escalation and dose escalation.Dose-escalation studies will be initiated by a dose-escalation study that selects the appropriate dose group seamlessly based on the data obtained (safety, clinical efficacy, PK data).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ASKB589 Injection ASKB589 Injection ASKB589 Injection treatment. This phase I/II trial will include two stages, a dose escalation stage and an expansion stage. |
Biological: ASKB589 Injection
ASKB589 Injection with dose escalation stage of 10mg/kg and 15mg/kg,as well as dose expansion stage with recommended dose level fro m dose escalation stage.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with adverse events as assessed by CTCAE v5.0 [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.
- The incidence and case number of DLT (Dose Limiting Toxicity) during observation period. [up to 21 days following last 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.
- Maximum Tolerated Dose (MTD） [up to 21 days following last 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 [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.
Secondary Outcome Measures
- Pharmacokinetics:maximum Plasma Concentration [Cmax] [Up to 21 days after injection]
Serum samples will be collected for Cmax analysis.
- Pharmacokinetics:time to maximum observed plasma concentration (Tmax) [Up to 21 days after injection]
Serum samples will be collected for Tmax analysis.
- Pharmacokinetics:elimination rate constant（Kel） [Up to 21 days after injection]
Serum samples will be collected for Kel analysis
- Pharmacokinetics:terminal elimination half life (T1/2) [Up to 21 days after injection]
Serum samples will be collected for T1/2 analysis.
- Pharmacokinetics:apparent volume of distribution (Vz/F) [Up to 21 days after injection]
Serum samples will be collected for Vz/F analysis.
- Pharmacokinetics:Area Under Curve (AUC) [Up to 21 days after injection]
Serum samples will be collected for AUC analysis.
- Pharmacokinetics: Mean ResidenceTime（MRT） [Up to 21 days after injection]
Serum samples will be collected for MRT analysis.
- Pharmacokinetics: plasma clearance rate (CL) [Up to 21 days after injection]
Serum samples will be collected for CL analysis.
- Pharmacokinetics: steady-state peak concentration (Css_max) [Up to 21 days after injection]
Serum samples will be collected for Css_max analysis.
- Pharmacokinetics: time to steady-state peak concentration (Tss_max) [Up to 21 days after injection]
Serum samples will be collected for Tss_max analysis.
- Pharmacokinetics: minimum value of steady plasma drug concentration（Css_min） [Up to 21 days after injection]
Serum samples will be collected for Css max analysis.
- Evaluation of immunogenicity [from date of treatment start until data cut-off, up to 2 years]
Incidence of anti-drug antibodies (ADA)
- 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]
Evaluation of objective response rate assessed by RECIST 1.1
- 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]
Evaluation of Disease control rate assessed by RECIST 1.1
- 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]
Duration of response assessed by RECIST 1.1
- 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]
Progression of tumor will be measured by RECIST v1.1
- Overall survival（OS） [from the date of treatment start until the documented date of death from any cause，up to 2 years.]
defined as the time from the date of treatment start until date of death due to any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histopathologically confirmed unresectable locally advanced, recurrent, or metastatic adenocarcinoma of the gastric and gastroesophageal junction currently ineligible for surgery and radical radiotherapy.
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Investigators determined that the present situation of the patient justifies chemotherapy plus immunotherapy as first-line treatment;or patients who progressed 6 months or more after neoadjuvant chemotherapy or after adjuvant chemotherapy.
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Tumor tissue samples are CLDN18.2 positive detected by central laboratory in Screening Phase.
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ECOG performance status (PS) 0-1.
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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) 6.Life expectancy of at least 3 months. 7.Specific Criteria
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Patients enrolled in the dose-escalation study also met the intermediate and high expression criteria for CLDN18.2.
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Participants in the dose-escalation study also had to satisfy at least one measurable lesion (based on RECIST v1.1 criteria).
Exclusion Criteria:
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Known active central nervous system (CNS) metastasis or suspected cancerous meningitis;
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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;
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The presence of clinically uncontrollable third interspace fluid (except ascites and chest fluid as described above) was judged by the investigator to be ineligible；
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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.
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Applicable to anti-HER-2 drug therapy；
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Anti-CLDN18.2 antibody, anti-PD-1 antibody, or drug therapy at any time in the past；
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Patients have received antitumor therapy including chemotherapy, radiotherapy, biologic therapy, endocrine therapy, targeted therapy, immunotherapy, and so on during the first 4 weeks before study drug use;
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Undergoing systemic pharmacotherapy with medicinal herbs or immunomodulatory agents with antitumor indications within 2 weeks of study drug initiation.
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Whole-blood,component-blood,or growth factor therapies in the first 2 weeks of study drug use.
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Systemic immunosuppression was performed within 2 weeks of the study drug's first use.Subjects were allowed physiological replacement doses of hydrocortisone or its equivalent and single sessions of systemic corticosteroids.
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Participation in clinical trials of other drugs in the first 4 weeks before study drug use.
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Major surgery was performed within 4 weeks of the study drug's first use or planned for major surgery during a clinical trial.
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Is known to be allergic to any monoclonal antibody or chemotherapeutic agent formulation.
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Gastrointestinal disorders caused by nonmalignant tumors (gastric adenocarcinoma, esophagogastric junction adenocarcinoma) such as gastrinoma, duodenitis, gastric ulcer, duodenal ulcer, and pancreatitis during the first 3 months of study drug use.
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Patients with irritable bowel syndrome, ulcerative colitis, Crohn's disease, gastric outlet obstruction, etc. or any other cause of prolonged chronic nausea, persistent recurrent vomiting or diarrhea, and uncontrolled or severe gastrointestinal bleeding as determined by investigators.
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Patients currently suffering from diseases that affect intravenous injection and venous blood sampling;
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Have a history of diagnosed neurological or mental disorders, including epilepsy or dementia;
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Patients with active infections such as HBV, HCV, HIV, and syphilis.
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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%； 20.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; 21.Patients who are not meet the inclusion criteria based on the judgment of investigator.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- AskGene Pharma, Inc.
- Jiangsu Aosaikang Pharmaceutical Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ASK-LC-B589- Ib/II