Clinical trial NCT04641754: A Study Evaluates the Safety and Efficacy of WX-0593 in ALK -Positive, or ROS1-positive Non-small Cell Lung Cancer
Official title: Phase II Clinical Study to Evaluate the Efficacy and Safety of WX-0593 in Patients With Crizotinib-resistant ALK -Positive, or Crizotinib-resistant/Crizotinib-naive ROS1-positive Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Qilu Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-24
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate safety and efficacy of WX-0593 oral tablets in ALK -positive, or ROS1-positive non-small cell lung cancer (NSCLC)

Detailed description: The clinical study is a single-arm, phase II, open label, multicenter design in patients with crizotinib-resistant ALK -positive, or crizotinib-resistant/crizotinib-naive ROS1-positive NSCLC.

Eligibility criteria: Inclusion Criteria:

1. ≥18 years.
2. Female or male;
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
4. Expected survival no less than 12 weeks.
5. Patient should have at least one measurable lesion (RECIST 1.1); Lesions previously treated with radiotherapy can be considered target lesions only if there is a clear evidence of progression after radiotherapy.
6. Histologically or cytologically confirmed advanced ALK-positive NSCLC in upper first-class hospitals，or histologically or cytologically confirmed advanced ROS1-positive NSCLC in a central laboratory. Admission of ROS1-positive patients will be based on the positive test results confirmed by the central laboratory or by the local-approved method.

   1. Patients with ALK-positive NSCLC who had been progressive disease after at least 12 weeks of continuous treatment with crizotinib .
   2. Patients with ROS1-positive NSCLC who failed in standard treatment (eg.resistant /intolerance of crizotinib or chemotherapy).
   3. Patients with ROS1-positive NSCLC who cannot accept chemotherapy.
   4. ROS1-positive NSCLC patients who could not afford crizotinib treatment.
7. Patients with or without asymptomatic CNS metastases, or symptomatic brain metastasis after treatment stabilized for more than 4 weeks, and with stopping systemic sex hormone therapy for more than 2 weeks.
8. Organ functions should meet the following requirements (Blood components, cell growth factors, drugs that stimulate the growth of WBC or platelets, or drugs used to correct anemia are not permitted within 14 days prior to the laboratory examination): ANC≥1.5\*10\^9/L PLT≥90\*10\^9/L,Hb≥90 g/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%.
9. Any surgery, prior radiotherapy (except for palliative radiotherapy)/procedures must be completed at least 4 weeks prior to starting the treatment with study drug. Palliative radiotherapy must be completed within 48 hours prior to starting treatment.
10. Subject understands and voluntarily provides informed consent.

Exclusion Criteria:

1. Received any prior ALK inhibitors other than crizotinib.
2. Patients with brain meningeal metastasis.
3. Any clinically significant cardiovascular disease within 6 months prior to the first dose of the investigational drug, including but not limited to: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident (including transient ischemic attack).
4. Two consecutive corrected QT interval (QTc) \> 480 ms through ECG examination during screening, patients with NCI-CTCAE v4.03 Grade ≥2 arrhythmia, Grade ≥2 heart failure, atrial fibrillation and ventricular fibrillation of any grade, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
5. Concomitant use of medications that may cause QTc prolongation or induce Torsades de pointes within 14 days prior to the first dose of the investigational drug or during treatment.
6. Continuous use of corticosteroids for more than 30 days, or require chronic use of corticosteroids or other immunosuppressants.
7. Past history of a large area of diffuse/interstitial pulmonary fibrosis, or known history of Grade 3 or 4 interstitial pulmonary fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonitis, interstitial lung disease, obliterative bronchiolitis, or pulmonary fibrosis, but does not include local radiation pneumonitis or radiation-induced pulmonary fibrosis.
8. Patients with Grade \> 1 nausea, vomiting, or diarrhea (CTCAE 4.03), other GI dysfunction or GI disease that may potentially affect drug absorption (such as ulcerative disease or malabsorption syndrome).
9. Subject received other clinical trial treatment within 1 month prior to the first dose of the investigational drug (if the medication received is a marketed drug, then refer to exclusion criteria #11).
10. Patients who are HBsAg-positive and/or HBcAb positive and HBV DNA \>10\^3 copies/mL, or HCV antibody-positive, or syphilis antibody- positive or known HIV infected.
11. No more than 2 weeks between the most recent use of another anti-cancer treatment (half life ≤3 days) and the first dose of the investigational drug, or the most recent use of another anti-cancer treatment (half life \> 3 days) is less than 4 weeks. Patients previously treated with crizotinib could take WX-0593 tables after 1 week from the last dose.
12. Patients who cannot suspend the use of a strong CYP3A4 inducer or inhibitor at least 1 weeks prior to this study and during the study. These drugs include but are not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin, rifapentine, tipranavir, ritonavir, St. John's wart, and ketoconazole.
13. Patients who cannot suspend the use of a CYP3A4 substrate at least 1 weeks prior to this study and during the study, and the therapeutic index is low.
14. Pregnant or lactating female patients or a positive pregnancy test at baseline for females of childbearing potential.
15. Childbearing potential female patients who are unwilling to use effective contraceptive measures during the entire course of the study and within 6 months after the end of the study, or male patients who plan to have children.
16. Concurrent diseases that may seriously affect patient safety or impact patient completion of the study as determined by the investigator (such as clinically uncontrolled hypertension (blood pressure \> 160/110 mmHg), severe diabetes, or thyroid disease).
17. Drug or alcohol abuse. Alcohol abuse refers to drinking 14 units of alcohol per week: 1 unit = 285mL of beer, or 25mL of spirits, or 100mL of wine.
18. History of definitive neurological or mental disorder, including epilepsy or dementia.
19. Patients with other malignant tumors within 3 years prior to screening (except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, thyroid carcinoma in situ, and papillary thyroid carcinoma).
20. Patients with added risks associated with the study or may interfere with the interpretation of study results as determined by the investigator, or deemed unsuitable by the investigator and/or sponsor.

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) Assessed By An Independent Review Committee
timeFrame: From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR) Assessed By Investigators
timeFrame: From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
measure: Progression-free survival (PFS)
timeFrame: From frist administration of WX-0593 until firstly recorded disease progression or death (whichever occurs earlier), or to the date that the last patients observed for 18 weeks.
measure: Disease Control Rate (DCR)
timeFrame: From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
measure: Duration of Response (DOR)
timeFrame: From frist administration of WX-0593 to the date that the last patients observed for 18 weeks .
measure: Time to Progression (TTP)
timeFrame: From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
measure: Confirmed Intracranial Objective Response Rate (iORR)
timeFrame: From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
measure: Overall Survival (OS)
timeFrame: From frist administration of WX-0593 until death due to any cause, withdraws informed consent, is lost to follow-up or refuses phone visits, or study completion（up to 2.5 years）
measure: Incidence of Adverse Events
timeFrame: the date of written informed consent signed until at least 28 days after the last dose of study drug was administered.
measure: Cssmin
timeFrame: Pre-dose on Cycle 1 Day 1, Cycle 1 Day 7, Cycle 1 Day 21, Cycle 2 Day 21, and Cycle 4 Day 21 (each cycle is 21 days)
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: Oncology Department, Anhui Cancer Hospital
state: Anhui
city: Hefei
country: China
facility: Respiratory Department, Anhui Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Thoracic Oncology I Department, Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Thoracic Oncology II Department, Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital
state: Beijing
city: Beijing
country: China
facility: General Department, Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Army Medical Center of PLA
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Lanzhou
country: China
facility: Gansu Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
state: Guangxi
city: Shijiangzhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Tumor Hospital
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nanjing
country: China
facility: Nanjing Chest Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Wuxi
country: China
facility: The Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: Tangdu Hospital
state: Shanxi
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Cancer Hospital Affiliated to Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Hangzhou first people's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: