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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

NCT04632108

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Carcinoma
  • Malignant Solid Tumor
  • Pancreatic Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: ASK-LC-B589-I/II
  • NCT ID: NCT04632108

Conditions

  • Malignant Solid Tumor

Interventions

DrugSynonymsArms
ASKB589 InjectionASKB589 Injection

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ASKB589 InjectionExperimental
  • ASKB589 Injection

Eligibility Criteria

        Inclusion Criteria:

          1. 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;

          2. ECOG performance status (PS) 0-1;

          3. 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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events as assessed by CTCAE v5.0
Time Frame:up to 21 days following last dose
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Pharmacokinetics:maximum Plasma Concentration [Cmax]
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for Cmax analysis.
Measure:Pharmacokinetics:time to maximum observed plasma concentration (Tmax)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for Tmax analysis.
Measure:Pharmacokinetics:elimination rate constant(Kel
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for Kel analysis.
Measure:Pharmacokinetics:terminal elimination half life (T1/2)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for T1/2 analysis.
Measure:Pharmacokinetics:apparent volume of distribution (Vz/F)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for Vz/F analysis.
Measure:Pharmacokinetics:Area Under Curve (AUC)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for AUC analysis.
Measure:Pharmacokinetics: Mean ResidenceTime(MRT)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for MRT analysis.
Measure:Pharmacokinetics: plasma clearance rate (CL)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for CL analysis.
Measure:Pharmacokinetics: steady-state peak concentration (Css_max)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for Css_max analysis.
Measure:Pharmacokinetics: time to steady-state peak concentration (Tss_max)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for Tss_max analysis.
Measure:Pharmacokinetics: minimum value of steady plasma drug concentration(Css_min)
Time Frame:Up to 21 days after injection
Safety Issue:
Description:Serum samples will be collected for Css max analysis.
Measure:Evaluation of immunogenicity
Time Frame:from date of treatment start until data cut-off, up to 2 years
Safety Issue:
Description:Incidence of anti-drug antibodies (ADA)
Measure:Objective response rate(ORR)
Time Frame:from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years
Safety Issue:
Description:Evaluation of objective response rate assessed by RECIST 1.1
Measure:disease control rate(DCR)
Time Frame:from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years
Safety Issue:
Description:Evaluation of Disease control rate assessed by RECIST 1.1
Measure:Duration of Response(DOR)
Time Frame:from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years
Safety Issue:
Description:Duration of response assessed by RECIST 1.1
Measure:Progression free survival(PFS)
Time Frame:from date of treatment start until the date of disease progression or until death due to any causes, up to 2 years.
Safety Issue:
Description:Progression of tumor will be measured by RECIST v1.1
Measure:Overall survival(OS)
Time Frame:from the date of treatment start until the documented date of death from any cause,up to 2 years.
Safety Issue:
Description:defined as the time from the date of treatment start until date of death due to any cause

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jiangsu Aosaikang Pharmaceutical Co., Ltd.

Last Updated

November 17, 2020