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

NCT04632758 | Unknown Phase 3

• 1 other identifier: WX0593-004
• Study Type: interventional
• Target: 292
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• Progression-free survival (PFS)

  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

  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

  From fist administration to the date that the last patients observed for 12 months

• Confirmed Objective Response Rate (ORR) Assessed By Investigators

  From fist administration to the date that the last patients observed for 12 months

• Time to Response (TTR) Assessed By independent radiology

  From fist administration to the date that the last patients observed for 12 months

Study Arms (2)

WX-0593 Tablets

EXPERIMENTAL

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

crizotinib

ACTIVE COMPARATOR

Eligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID without food until documented disease progression or unacceptable toxicity.

Drug: crizotinib

Interventions

WX-0593 Tablets DRUG

tablets, 60 mg→180mg, QD

Also known as: FL-006

WX-0593 Tablets

crizotinib DRUG

Capsules, 250mg, BID

crizotinib

Eligibility Criteria

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

You may qualify if:

• ≥18 years
• Female or male
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Life expectancy of at least 12 weeks.
• At least one measurable lesion (according to RECIST v1.1)
• 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.
• 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
• 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%.
• 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.
• Patients must be able to understand and volunteer to sign the informed consent.

You may not qualify if:

• Patients that have previously received cancer therapy (i.e., other targeted therapies, chemotherapy, immunotherapy, biologic therapy, hormonal therapy).
• Patients with tumor meningeal metastasis
• Clinically significant cardiovascular disease within 6 months prior to first dosing.
• 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
• 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.
• Continuous use of corticosteroids for more than 30 days, or require chronic use of corticosteroids or other immunosuppressants
• 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.
• Patients with Grade \> 1 nausea, vomiting, or diarrhea (CTCAE 4.03), other GI dysfunction or GI disease that may potentially affect drug absorption.
• Patients at risk for GI perforation or intestinal obstruction
• 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.
• 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.
• 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.
• 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.
• Females who are pregnant or breastfeeding. Pregnant or lactating female patients or a positive pregnancy test at baseline for females of 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.

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Location

Related Publications (1)

• Shi Y, Chen J, Yang R, Wu H, Wang Z, Yang W, Cui J, Zhang Y, Liu C, Cheng Y, Liu Y, Shan J, Wang D, Yang L, Hu C, Zhao J, Cao R, Tan B, Xu K, Si M, Li H, Mao R, Li L, Kang X, Wang L. Iruplinalkib (WX-0593) Versus Crizotinib in ALK TKI-Naive Locally Advanced or Metastatic ALK-Positive NSCLC: Interim Analysis of a Randomized, Open-Label, Phase 3 Study (INSPIRE). J Thorac Oncol. 2024 Jun;19(6):912-927. doi: 10.1016/j.jtho.2024.01.013. Epub 2024 Jan 25.

  PMID: 38280448 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Crizotinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2020
• First Posted: November 17, 2020
• Study Start: June 1, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 24, 2023

Record last verified: 2023-11

Locations

CN (1)