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The purpose of the study is to evaluate safety, pharmacokinetics and efficacy of WX-0593 alone in the treatment of advanced cancer.
The first part is a single-arm, phase 1, open label, dose-escalation design in patients with anaplastic lymphoma kinase(ALK)/receptor tyrosine kinase(ROS1) Positive ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in anaplastic lymphoma kinase(ALK) expression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| WX-0593 Tablets | Experimental | The first part is a dose-escalation design in patients with ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in ALK expression. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| WX-0593 Tablets | Drug | tablets, dosage ranged from 30 mg to 300 mg, quaque die(QD) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose(MTD) | The MTD is determined by the number of the participants in cohort who suffer a dose-limiting toxicity (DLT). The MTD is defined as the former dose at which more than one third of the participants develop a DLT. If no DLTs are observed, the MTD is not reached. | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Tmax of WX-0593 | Pharmacokinetics of WX-0593 by assessment of time to Cmax | 28 days |
| Cmax of WX-0593 | Pharmacokinetics of WX-0593 by assessment of maximum plasma WX-0593 concentration. |
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Inclusion Criteria:
18 to 70 years, inclusive.
Female or male
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Life expectancy of at least 12 weeks.
At least one measurable lesion (according to RECIST v1.1)
Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy with ALK/ROS1+ (For the expansion phase, patients must have NSCLC with ALK+ ):
Patients with treated or untreated asymptomatic Central Nervous System(CNS) metastases may be allowed to enroll.
Patients must have normal function as defined: ANC≥1.5*10^9/L PLT≥100*10^9/L, Total Bilirubin (TBIL)≤1.5*Upper Limit of Normal(ULN) ( Gilbert's Syndrome TBIL ≤3.0*ULN and DBIL≤1.5*ULN ),Alanine Transaminase (ALT)and Aspartate Aminotransferase(AST)≤2.5*ULN. For liver metastasis patients, ALT and AST≤5*ULN, Cr≤1.5*ULN, LVEF≥50%.
Any surgery or radiation (expect for palliative radiation) must have been completed at least 4 weeks prior to first dosing. Palliative radiation must have been completed at least 48 hours prior to first dosing.
All related adverse events from previous anti-cancer therapies must have recovered to ≤ Grade 1 (except for alopecia).
Patients must be able to understand and volunteer to sign the informed consent.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yuankai Shi, M.D. | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Principal Investigator |
| Jian Fang, M.D. | Peking University Cancer Hospital & Institute | Principal Investigator |
| Shucai Zhang, M.D. | Beijing Chest Hospital, Capital Medical University | Principal Investigator |
| Yunpeng Liu, M.D. | First Hospital of China Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Recruiting | Beijing | Beijing Municipality | 100021 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40650620 | Derived | Yang G, Wang Y, Zhao H, Zheng Q, Wang X, Jia L, Xin Q, Ma C, Zhang Y, Zheng S, Kang X. Translational Model-Informed Dose Selection for Iruplinalkib, a Selective Oral ALK/ROS1 Tyrosine Kinase Inhibitor. Clin Transl Sci. 2025 Jul;18(7):e70287. doi: 10.1111/cts.70287. | |
| 35087031 | Derived | Shi Y, Fang J, Hao X, Zhang S, Liu Y, Wang L, Chen J, Hu Y, Hang X, Li J, Liu C, Zhang Y, Wang Z, Hu Y, Gu K, Huang J, Zhang L, Shan J, Ouyang W, Zhao Y, Zhuang W, Yu Y, Zhao J, Zhang H, Lu P, Li W, Si M, Ge M, Geng H. Safety and activity of WX-0593 (Iruplinalkib) in patients with ALK- or ROS1-rearranged advanced non-small cell lung cancer: a phase 1 dose-escalation and dose-expansion trial. Signal Transduct Target Ther. 2022 Jan 28;7(1):25. doi: 10.1038/s41392-021-00841-8. |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| 28 days |
| Cmin of WX-0593 | Pharmacokinetics of WX-0593 by assessment of minimum plasma WX-0593 concentration. | 28 days |
| AUC of WX-0593 | Pharmacokinetics of WX-0593 by assessment of area under the plasma concentration time curve from zero to infinity | 28 days |
| tl/2 of WX-0593 | Pharmacokinetics of WX-0593 by assessment of the terminal half-life | 28 days |
| Cssmin of WX-0593 | Cmin of WX-0593 at steady state | 28 days |
| Cssmax of WX-0593 | Cmax of WX-0593 at steady state | 28 days |
| Css-av of WX-0593 | Mean plasma concentration of WX-0593 at steady state | 28 days |
| AUCss of WX-0593 | area under the curve of WX-0593 at steady state | 28 days |
| DF of WX-0593 | Pharmacokinetics of WX-0593 by assessment of degree of fluctuation | 28 days |
| Vz of WX-0593 | volume of distribution during terminal phase after WX-0593 administration | 28 days |
| CLs of WX-0593 | total plasma,serum or blood clearance of WX-0593 after administration | 28 days |
| Objective Response Rate (ORR) | Primary efficacy endpoint is a change in the proportion of subjects showing overall objective response rate (ORR) from baseline to final tumor assessment point after treatment. As Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the percentage of subjects indicating PR (partial response) and CR (complete response) will be calculated. According to RECIST 1.1 criteria, complete response (CR) - the disappearance of all target lesions and partial response ( PR ) - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. | From fist administration of WX-0593 to 28 days after last medication. |
| Progression-free survival (PFS) | PFS defined as the time from baseline to first observed disease progression or death from any cause. | From fist administration of WX-0593 to 28 days after last medication. |
| Disease Control Rate (DCR) | DCR is the percentage of patients with best response of CR, PR or Stable Disease (SD). SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter. | From fist administration of WX-0593 to 28 days after last medication. |
| Duration of Response (DOR) and so on | The DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date on which progressive disease (PD) is first noted or date of death. | From fist administration of WX-0593 to 28 days after last medication. |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |