Study Comparing WX-0593 to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients

An Open-label, Randomized, Multicenter Phase 3 Study Comparing WX-0593 to Crizotinib in Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC) Patients

The primary purpose of this study is to evaluate the efficacy and safety of WX-0593 vs. crizotinib in patients with ALK-positive non-small cell lung cancer who had not received prior systemic therapy

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: WX-0593 Tablets; Drug: crizotinib

Detailed Description

To evaluate the efficacy and safety of WX-0593 vs. crizotinib in patients with ALK-positive NSCLC who had not received prior systemic therapy, to obtain additional pharmacokinetic (PK) data from sparse PK sampling, to compare the quality of life (QoL) in patients receiving WX-0593 vs. crizotinib, to evaluate the status of exploratory biomarkers and correlate with clinical outcome, and to obtain germline DNA samples for possible pharmacogenetic analysis in the event that outliers with respect to efficacy, tolerability/safety, or exposure are identified.

• Study Type: Interventional
• Enrollment (Anticipated): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      • Contact: Yuankai Shi, M.D.; Phone Number: 010-67781331; Email: syuankaipumc@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥18 years
2. Female or male
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
4. Life expectancy of at least 12 weeks.
5. At least one measurable lesion (according to RECIST v1.1)
6. Histologically or cytologically confirmed diagnosis of advanced or recurrent or metastatic NSCLC that is ALK-positive by an Abbott FISH assay in the central lab. Randomization will occur after ALK positive confirmation is received from the central lab or local test using an method including Abbott FISH、RT-PCR or Ventana IHC.
7. No brain metastasis, or asymptomatic brain metastasis, or symptomatic brain metastasis but stable for more than 4 weeks after treatment, and have stopped systemic hormone treatment (prednisone of > 10 mg/day or equivalent hormone) for more than 2 weeks
8. Patients must have normal function as defined: 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 or prior radiation (expect for palliative radiation) /operations 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.
10. Patients must be able to understand and volunteer to sign the informed consent.

Exclusion Criteria:

1. Patients that have previously received cancer therapy (i.e., other targeted therapies, chemotherapy, immunotherapy, biologic therapy, hormonal therapy).
2. Patients with tumor meningeal metastasis
3. Clinically significant cardiovascular disease within 6 months prior to first dosing.
4. Two consecutive corrected QT interval (QTc) > 480 ms through ECG examination during screening, ≥2 arrhythmias, ≥2 heart failure (according to CTCAE 4.03), atrial fibrillation and ventricular fibrillation of any grade, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention
5. 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.
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.
8. Patients with Grade > 1 nausea, vomiting, or diarrhea (CTCAE 4.03), other GI dysfunction or GI disease that may potentially affect drug absorption.
9. Patients at risk for GI perforation or intestinal obstruction
10. Patient has received other investigational drug within 1 month prior to first dosing. Subject received other clinical trial treatment within 1 month prior to the first dose of the investigational drug.
11. Patients who are HBsAg-positive and/or HBcAB positive and HBV DNA > 103copies/mL, or HCV antibody-positive, or syphilis antibody- positive or known HIV infected.
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.
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. Females who are pregnant or breastfeeding. Pregnant or lactating female patients or a positive pregnancy test at baseline for females of childbearing potential.
15. 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 abusers and alcoholics. 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 5 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: WX-0593 Tablets; Eligible patients with ALK+ NSCLC will receive WX-0593 tablets without food until documented disease progression or unacceptable toxicity. 60 mg of WX-0593 tablets, once daily for 7 days, followed by 180 mg of WX-0593 tablets, once daily in a 28-days cycle.	Drug: WX-0593 Tablets; tablets, 60 mg→180mg, QD; Other Names: FL-006
ACTIVE_COMPARATOR: crizotinib; Eligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID without food until documented disease progression or unacceptable toxicity.	Drug: crizotinib; Capsules, 250mg, BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS as assessed by independent radiology review based on RECIST v. 1.1 criteria	from randomization until firstly recorded disease progression or death (whichever occurs earlier), or to the date that the last patients observed for 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS based on investigator assessment	from randomization until firstly recorded disease progression or death (whichever occurs earlier), or to the date that the last patients observed for 12 months
OS	Overall survival (OS)	from randomization 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）
Confirmed Objective Response Rate (ORR) Assessed By independent radiology review	ORR is defined the percentage of the participants who have achieved complete response (CR) or partial response (PR) per independent radiology review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after the initiation of study treatment.	From fist administration to the date that the last patients observed for 12 months
Confirmed Objective Response Rate (ORR) Assessed By Investigators	ORR is defined the percentage of the participants who have achieved complete response (CR) or partial response (PR) per Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after the initiation of study treatment.	From fist administration to the date that the last patients observed for 12 months
Time to Response (TTR) Assessed By independent radiology	Assessed from date of the first dose until the date of progression per independent radiology review	From fist administration to the date that the last patients observed for 12 months
Time to Response (TTR) Assessed By Investigators	Assessed from date of the first dose until the date of progression per investigator.	From fist administration to the date that the last patients observed for 12 months
Duration of response (DOR) Assessed By independent radiology	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 to the date that the last patients observed for 12 months
Duration of response (DOR) Assessed By Investigators	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 to the date that the last patients observed for 12 months
CNS response rate based on independent radiology review	CNS response rate based on independent radiology review	From fist administration to the date that the last patients observed for 12 months
CNS response rate based on investigator assessment	CNS response rate based on investigator assessment	From fist administration to the date that the last patients observed for 12 months
Time to CNS progression	Time to CNS progression	From fist administration to the date that the last patients observed for 12 months
Percentage of patients with adverse events	the incidence of adverse events, including adverse events (AEs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs). Causality is determined by the investigator.	from the signing of the informed consent form until at least 28 days after the last dose of study drug was administered.
Plasma concentrations (Cssmin)	Minimum value of steady plasma-drug concentration for WX-0593 at participating sites	Cssmin before dosing on Cycle 1 Day 1, Cycle 1 Day 7, Cycle 1 Day 21, Cycle 2 Day 21, and Cycle 4 Day 21
Patient reported time to deterioration (TTD)	Patient reported time to deterioration (TTD) as measured by EORTC C30/LC13 QoL questionnaire	From fist administration to the date that the last patients observed for 12 months
Patient reported time to deterioration (TTD)	Patient reported time to deterioration (TTD) as measured by Lung Cancer Symptom Scale (LCSS) questionnaire	From fist administration to the date that the last patients observed for 12 months
Patient reported health-related quality of life (HRQoL)	Patient reported health-related quality of life (HRQoL) as measured by EORTC C30/LC13 QoL questionnaire	From fist administration to the date that the last patients observed for 12 months
Patient reported health-related quality of life (HRQoL)	Patient reported health-related quality of life (HRQoL) as measured by Lung Cancer Symptom Scale (LCSS) questionnaire	From fist administration to the date that the last patients observed for 12 months

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2019
• Primary Completion (ANTICIPATED): June 1, 2021
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: September 5, 2020
• First Submitted That Met QC Criteria: November 11, 2020
• First Posted (ACTUAL): November 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: WX0593-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No