Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of ASKC202

Study Overview
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Brief Summary
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This study is the first-in-human of ASKC202, which is an open-label, non-randomized, multicenter study with a dose escalation phase and a dose expansion phase.

Official Title
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A Phase I ,Open, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of ASKC202 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: ASKC202


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide signed and dated informed consent; Aged 18 years old or more, male or female; The subjects with locally advanced or metastatic solid tumors for whom no standard therapy regimens are available currently or who are intolerable to standard therapy regimens; dose extension study: The subjects with MET gene amplification or protein overexpression solid tumors (IHC 2+ or 3+) confirmed by the central laboratory will be enrolled. At least one measurable lesion (based on the RECIST 1.1 criterion) (this article is only for the dose expansion phase); ECOG score 0 1; Expected survival time ≥ 3 months; Major organ function is essentially normal (no transfusions, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), or other medically supportive care have been received in the 14 days prior to the administration of the study drug), and laboratory tests during the screening period meet the following criteria: system Laboratory test values haematology Absolute neutrophil count ≥1.5 ×109/L platelet ≥90×109/L haemoglobin ≥90g/L kidney Serum creatinine or Creatinine clearance (CrCl). ≤ 1.5 × ULN or ≥60 mL/min (estimated from the Cockcroft-Gault formula) liver Total bilirubin ≤1.5 × ULN or ≤2 × ULN (for patients with liver cancer or liver metastases). AST(SGOT) and ALT (SGPT). ≤2.5 × ULN or ≤5 × ULN (for patients with liver cancer or liver metastases). Coagulation (no anticoagulation was received in the 7 days prior to the administration of the study drug). International normalized ratio (INR) or prothrombin time (PT). ≤1.5 × ULN Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN Women of childbearing age must have a pregnancy test (serum or urine) within 7 days of enrolling and have a negative result, or meet one of the following criteria to prove that there is no risk of pregnancy: a Postmenopausal is defined as amenorrhea at least 12 months after age >50 years and discontinuation of all exogenous hormone replacement therapy; b Women younger than 50 years of age who are considered postmenopausal if they have been amenorrhea for 12 months or more after stopping all exogenous hormone therapy, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the laboratory reference values for postmenopausal; c Previously undergone irreversible sterilization procedures, including hysterectomy, bilateral ovarian resection, or bilateral salping, with the exception of bilateral tubal ligation; Women of childbearing age should use strict contraceptive contraception throughout trial 7 and within 3 months after the last dose of the test drug; male subjects should use strict contraception throughout the trial period and for 6 months after the last dose of the test drug and no sperm donation; The patient understands the purpose and steps of the trial, voluntarily participates in the trial, and signs a written informed consent form; Patients have good comprehension, are able to follow protocol requirements and can cooperate with investigators in this trial. Exclusion Criteria: Have previously received or are receiving any treatment for c-Mets (including all monoclonal antibodies or small molecule drugs targeted at the target); Have received chemotherapy, hormone therapy, immunotherapy, or biological therapy such as antibody therapy within 4 weeks prior to the first dose, or traditional Chinese medicine with anti-tumor indications within 2 weeks, or small molecule targeted therapy with an interval of less than 5 half-lives Those who still need to continue to use systemic immunosuppressants or systemic corticosteroids (≥ 10 mg of prednisone or its equivalent other corticosteroid) for 2 weeks prior to the first dose; Patients who have used strong inhibitors or strong inducers of CYP3A within 2 weeks prior to the first administration, or who need to continue treatment with these drugs during the study period; Participation in clinical trials of other drugs within 4 weeks prior to the first administration (except for failed screening); Patients who underwent other major surgical procedures other than diagnosis or biopsy within 4 weeks prior to the first dose, or who were expected to undergo major surgeries during the study period; Prior to the first administration, there are unhealed toxic reactions of ≥ grade 2 (CTCAE 5.0 standard) associated with any previous treatment, any level of hair loss, and platinum drugs Except for grade 2 neuropathy caused; Patients with primary central nervous system tumors or central nervous system metastases including meningeal metastases (except those who are asymptomatic and stable, do not require steroid use for at least 4 weeks before the first dose); Gastrointestinal disorders (e.g., Crohn's disease, ulcerative colitis, intestinal obstruction, short bowel syndrome) or other malabsorption conditions that have difficulty swallowing or affect drug absorption; There are any other serious or uncontrolled acute and chronic diseases, such as severe or uncontrollable liver or kidney disease (except liver and kidney cancer), uncontrollable hypertension (blood pressure > 150/95 mmHg after antihypertensive therapy), and Acute pancreatitis, uncontrollable hyperglycemia (fasting blood glucose >8.0 mmol/L after hypoglycemic therapy), severe or uncontrolled eye lesions, etc Previous history includes interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid therapy, or evidence of clinically active ILD Have previously received hematopoietic stem cell transplants or solid organ transplants, or plan to receive hematopoietic stem cell transplants or solid organ transplants during the current period of study; Imaging (CT or MRI) showing tumor invasion of large blood vessels in patients; If not controlled, large pleural effusions, pericardial effusions, or ascites that need to be drained still need; There are serious or active infections that required intravenous antibiotics or hospitalization, such as HBV (HBsAg-positive and peripheral HBV-DNA titer test≥1×104 copies/mL or 2000 IU/mL), HCV, HIV, and syphilis Meets any of the following cardiac criteria: a Average QTc interval prolongation of 3 ECG examinations at rest (QTcF: 450 ms> for men > 470 ms for women, corrected by Fredericcia's formula); b Presence of uncontrolled or symptomatic arrhythmias, familial arrhythmias, or congenital long QT syndromes; c Had undergone coronary angioplasty, stent implantation, and coronary artery bypass grafting within 6 months before admission; d Myocardial ischemia or myocardial infarction, unstable angina within 6 months before admission; e Judged to be class III-IV congestive heart failure according to the New York Heart Association's cardiac function grade; f Echocardiography (ECHO) shows a left ventricular ejection fraction (LVEF) ≤ 50%; allergies, or a previous history of severe allergies, or known allergies to any of the components of the drug under study; Pregnant, Lactating women; Other primary malignancies have been diagnosed within the last 5 years, and the following conditions can be enrolled: non-melanoma skin cancer, superficial bladder cancer, cervical carcinoma in situ that has undergone surgery and has been cured; Alcohol abuse, substance abuse, and other conditions that may increase the risk of the study or may interfere with study execution and analysis of results, or that the investigator believes that there are other reasons for which they are not suitable for this clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASKC202<br>Participants received ASKC2020 50mg 600mg orally | Drug: ASKC202<br>* Dosage Forms: Tablets; Administration: Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and case number of DLT (Dose Limiting Toxicity) during observation period | 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. | up to 21 days following first dose | 
| Maximum Tolerated Dose (MTD） | The MTD was defined as the highest dose of ASKC202 not causing DLT in more than 33% of patients in the first treatment cycle. | up to 21 days following first dose | 
| Number of participants with adverse events and serious adverse events as assessed by CTCAE v5.0 | An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported. | up to 30 days following last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics:maximum Plasma Concentration [Cmax] | Serum samples will be collected for Cmax analysis. | up to 21 days following first dose | 
| Pharmacokinetics:terminal elimination half life (T1/2) | Serum samples will be collected for T1/2 analysis. | up to 21 days following first dose | 
| Pharmacokinetics:Area Under Curve (AUC) | Serum samples will be collected for AUC analysis. | up to 21 days following first dose |