The Safety and Efficacy of Multiple-dose of WJ01024 in Subject With Advanced Cancer

Study Overview
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Brief Summary
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A clinical study of WJ01024 in subjects with advanced cancer in China, to evaluate the safety, tolerability, PK and efficacy of WJ01024. This study includes a dose escalation part and a dose expansion part. Patients receive WJ01024 on Day 1 and Day 3 of each week, 4 weeks as a cycle, until disease progression, or intolerable toxicity , withdrawal of consent, or end of the study, whichever occurs first.

Official Title
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A Dose Escalation and Dose Expansion Study of WJ01024 to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy for Patients With Advanced Cancer

Conditions
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Advanced Hematologic Malignancies, Advanced Solid Tumors

Intervention / Treatment
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* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024
* Drug: WJ01024


Participation Criteria
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Eligibility Criteria
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Inclusion criteria： Patients with advanced malignant neoplasms definitively diagnosed by pathology and/or cytology who have failed to respond to conventional treatment or are lacking effective treatment; For patients with solid tumors, there should be evaluable or measurable tumor lesions according to RECIST 1.1 criteria (not for dose-climbing phase); Males and females ≥ 18 and ≤ 70 years of age,ECOG performance status of 0 1; Life expectancy ≥3 months; The functions of the major organs were basically normal, and the following laboratory tests were performed within 7 days before the first administration of the study drug (no blood transfusion or colony-stimulating factor was administered within 14 days before the examination); For premenopausal women who are likely to have children, a pregnancy test must be performed within 7 days before the first use of the study drug. The blood pregnancy test must be negative and must be non-lactating.All enrolled patients (both male and female) should take adequate barrier contraception throughout the treatment period and 3 months after the end of treatment; Voluntary participant in this drug clinical trial, able to understand and sign the informed consent. Exclusion criteria Pregnant or lactating women; Suffer from other serious complications (such as uncontrolled infection, myocardial infarction within 6 months, uncontrolled hypertension and thromboembolic disease); There was active graft rejection at the time of enrollment (after allogeneic stem cell transplantation); Who is not suitable for the study after laboratory examination (blood routine, urine routine, blood biochemical, blood coagulation function) or as judged by the study physician; ≥ Grade 2 toxicity after previous treatment; Patients with grade 2 or more neuropathy; A person suffering from an uncontrollable mental illness; Have a history of drug abuse or urine drug screening positive; Heart disease: New York heart association (NYHA) > class II congestive heart failure, unstable angina (resting angina symptoms), new angina (within 6 months before entering the study), into the group of the first six months of myocardial infarction, or need anti-arrhythmic treatment for arrhythmia (allows the use of beta blockers, calcium channel blockers and digoxin); Alcoholics or those who consume more than 28 units of alcohol per week (1 unit = 285 mL beer or 25 mL spirits (40%v/v) or 1 glass [100ml] of wine); Patients with active hepatitis B, hepatitis C, HIV (+) and syphilis antibody (+);Patients with HBsAg or core antibody (HBcAb) positivity need to be tested for HBV-DNA, and HBV-DNA is lower than the upper limit of normal to be enrolled.Patients with hepatitis C virus antibody (HCV Ab) positive should be tested for HCV RNA, and those below the upper limit of normal can be enrolled. Requiring long-term corticosteroids or other immunosuppressive therapy, such as those who have had organ transplants; Other conditions considered ineligible by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WJ01024 5mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 5mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 10mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 10mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 20mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 20mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 40mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 40mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 60mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 60mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 80mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 80mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 100mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 100mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 120mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 120mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 140mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 140mg: WJ01024, Q4W, twice per week<br>|
| Experimental: WJ01024 160mg repeat dose every 28 days<br> | Drug: WJ01024<br>* 1600mg: WJ01024, Q4W, twice per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events (AE) and serious adverse events (SAE) were assessed | Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in vital signs, electrocardiogram, and laboratory tests | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | DLT, MTD, RP2D, Number of participants and severity with treatment-related Adverse events as assessed by CTCAE V5.0 | 2 years | 
| DOR | Duration of Response | 2 years | 
| DCR | Disease Control Rate | 2 years | 
| PFS | Progression-free survival | 2 years | 
| Cmax | Maximum Plasma Concentration | 2 years | 
| Tmax | Time to Cmax | 2 years | 
| AUC0-t | Area under the concentration versus time curve from time 0 to the last measurable concentration | 2 years | 
| AUC0-inf | AUC from time 0 to infinity | 2 years | 
| Kel | Elimination rate constant | 2 years | 
| t1/2 | Elimination half life time | 2 years | 
| CL/F | Clearance | 2 years | 
| Vd/F | Apparent volume of distribution | 2 years | 
| Rac | Accumulation factor | 2 years |