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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04632108
Recruitment Status : Not yet recruiting
First Posted : November 17, 2020
Last Update Posted : November 17, 2020
Sponsor:
Collaborator:
Jiangsu Aosaikang Biomedicine Co. LTD.
Information provided by (Responsible Party):
Jiangsu Aosaikang Pharmaceutical Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Malignant Solid Tumor Drug: ASKB589 Injection Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 214 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 15, 2020
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : November 1, 2022

Arm Intervention/treatment
Experimental: ASKB589 Injection Drug: ASKB589 Injection
Patients are given ASKB589 at 5 dose group: 0.3mg/kg,1mg/kg,3mg/kg,6mg/kg,10mg/kg




Primary Outcome Measures :
  1. 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.

  2. 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; h.) Is a new cancer (that is not a condition of the study) or i.) Is associated with an overdose. The number of participants who experience an SAE will be presented.

  3. The incidence and case number of DLT (Dose Limiting Toxicity) during observation period [ Time Frame: up to 21 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.

  4. Maximum Tolerated Dose (MTD) [ Time Frame: up to 21days 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.

  5. 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.

  6. 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 Outcome Measures :
  1. Pharmacokinetics:maximum Plasma Concentration [Cmax] [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for Cmax analysis.

  2. Pharmacokinetics:time to maximum observed plasma concentration (Tmax) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for Tmax analysis.

  3. Pharmacokinetics:elimination rate constant(Kel) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for Kel analysis.

  4. Pharmacokinetics:terminal elimination half life (T1/2) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for T1/2 analysis.

  5. Pharmacokinetics:apparent volume of distribution (Vz/F) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for Vz/F analysis.

  6. Pharmacokinetics:Area Under Curve (AUC) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for AUC analysis.

  7. Pharmacokinetics: Mean ResidenceTime(MRT) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for MRT analysis.

  8. Pharmacokinetics: plasma clearance rate (CL) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for CL analysis.

  9. Pharmacokinetics: steady-state peak concentration (Css_max) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for Css_max analysis.

  10. Pharmacokinetics: time to steady-state peak concentration (Tss_max) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for Tss_max analysis.

  11. Pharmacokinetics: minimum value of steady plasma drug concentration(Css_min) [ Time Frame: Up to 21 days after injection ]
    Serum samples will be collected for Css max analysis.

  12. Evaluation of immunogenicity [ Time Frame: from date of treatment start until data cut-off, up to 2 years ]
    Incidence of anti-drug antibodies (ADA)

  13. 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 ]
    Evaluation of objective response rate assessed by RECIST 1.1

  14. 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 ]
    Evaluation of Disease control rate assessed by RECIST 1.1

  15. 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 ]
    Duration of response assessed by RECIST 1.1

  16. 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. ]
    Progression of tumor will be measured by RECIST v1.1

  17. Overall survival(OS) [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04632108


Contacts
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Contact: ke ke Wang 025-85090621 15850644920@163.com

Sponsors and Collaborators
Jiangsu Aosaikang Pharmaceutical Co., Ltd.
Jiangsu Aosaikang Biomedicine Co. LTD.
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Responsible Party: Jiangsu Aosaikang Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT04632108    
Other Study ID Numbers: ASK-LC-B589-I/II
First Posted: November 17, 2020    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms