A Study Evaluates the Safety, Pharmacokinetics and Efficacy of WX-0593 in Advanced Solid Tumor Patients

NCT03389815 | Unknown Phase 1

• 1 other identifier: WX0593-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate safety, pharmacokinetics and efficacy of WX-0593 alone in the treatment of advanced cancer.

Conditions

Advanced Solid Tumor, Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (16)

• Tmax of WX-0593

  28 days

• Cmax of WX-0593

  28 days

• Cmin of WX-0593

  28 days

• AUC of WX-0593

  28 days

• tl/2 of WX-0593

  28 days

Study Arms (1)

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.

Drug: WX-0593 Tablets

Interventions

WX-0593 Tablets DRUG

tablets, dosage ranged from 30 mg to 300 mg, quaque die（QD）

Also known as: FL-006

WX-0593 Tablets

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 advanced tumor (eg. NSCLC, lymphoma, inflammatory myofibroblastic tumor) who failed in standard treatment (eg. resistant of ALK inhibitors or chemotherapy)
• Patients with advanced NSCLC who cannot accept chemotherapy or intolerance with chemotherapy.
• Advanced NSCLC patients who could not afford ALK inhibitor treatment.
• 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.

You may not qualify if:

• Clinically significant cardiovascular disease within 3 months prior to first dosing.
• Ongoing cardiac dysrhythmias, or any grade of uncontrolled atrial fibrillation, or prolonged QT interval (QTc \> 480 ms).
• Patients need medications that may prolong QT interval or induce torsades de pointes within 14 days prior to the first dosing or during the study.
• Peripheral neuropathy ≥ Grade 3 according to CTCAE 4.03.
• Patients who received continuous use of steroids for more than 30 days, or who need long-term use of steroid hormones or other immunosuppressive agents.
• History of extensive disseminated/bilateral pulmonary interstitial fibrosis, interstitial fibrosis or interstitial lung disease of Grade 3/4 .
• Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of WX-0593.
• Patients who are receiving warfarin sodium (Coumadin) or any other coumadin-derived anticoagulants，and patients with coagulation disturbance and bleeding tendency.
• Patient has received other investigational drug within 1 month.
• Patients with acute or chronic infectious medical conditions, including active hepatitis (Hepatitis A、 Hepatitis B、 Hepatitis C ) or HIV infection.
• Patients who received prior anti-cancer therapy within 2 weeks (t1/2 ≤ 3 days) or within 4 weeks (3 days \< t1/2）. Patients previously treated with crizotinib could start WX-0593 dosing after 1 week from the last dosing.
• Patients who could not discontinue therapy with potent CYP3A4 inhibitors or inducers within 1 week prior first dosing, or patients who need therapy with CYP3A4 inhibitors or inducers during the study.
• Patients received medications known to be metabolized by CYP3A4 and with narrow therapeutic indices, who could not discontinue within 1 week prior to the start of WX-0593 administration. Patients who need therapy with those medications during the study.
• Females who are pregnant or breastfeeding.
• Patients with childbearing potential must agree to use adequate contraception for the duration of treatment and for 6 months after the study.

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 40650620 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.

  PMID: 35087031 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2017
• First Posted: January 4, 2018
• Study Start: September 14, 2017
• Primary Completion: June 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 4, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)