Non-small Cell Lung CancerPhase 3NCT04632758
Study Comparing WX-0593 to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients
A Phase 3 study testing WX-0593 Tablets and crizotinib in people with Non-small Cell Lung Cancer, run by Qilu Pharmaceutical Co., Ltd. at 1 site in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- WX-0593 Tablets and crizotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 292 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2019to 1 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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.
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- 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.
Who cannot join
- 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
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- 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.
- 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).
- 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;
- History of definitive neurological or mental disorder, including epilepsy or dementia
- 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).
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality
About this study
Official title: 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
Read the 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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- WX-0593 Tablets, crizotinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WX-0593 TabletsDrug
Also called FL-006
tablets, 60 mg→180mg, QD
crizotinibDrug
Capsules, 250mg, BID
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: crizotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
PFS as assessed by independent radiology review based on RECIST v. 1.1 criteria
Measured: 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)
PFS based on investigator assessment
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: From fist administration to the date that the last patients observed for 12 months
Time to CNS progression
Time to CNS progression
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From fist administration to the date that the last patients observed for 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2020
- Study start1 Jun 2019
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Qilu Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 292 participants (actual)
Sponsor and investigators
- Lead sponsor
- Qilu Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04632758
- Sponsor's protocol ID
- WX0593-004
- Status last verified
- Nov 2023
- First submitted
- 5 Sep 2020
- Last updated
- 24 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38280448
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04632758
- Acronym / sponsor ID
- WX0593-004
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 292 participants (actual)
- Lead sponsor
- Qilu Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Jun 2019 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 17 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| WX-0593 Tablets | Experimental | Drug: WX-0593 TabletsEligible 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. |
| crizotinib | Active comparator | Drug: crizotinibEligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID without food until documented disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ≥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)
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WX-0593 TabletsAlso: FL-006tablets, 60 mg→180mg, QD | Drug | WX-0593 Tablets |
| crizotinibCapsules, 250mg, BID | Drug | crizotinib |
Primary outcome
Progression-free Survival (PFS)
Time frame: from randomization until firstly recorded disease progression or death (whichever occurs earlier), or to the date that the last patients observed for 12 months
PFS as assessed by independent radiology review based on RECIST v. 1.1 criteria
17 secondary outcomes
Progression-free survival (PFS)
Time frame: 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
Time frame: 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
Time frame: From fist administration to the date that the last patients observed for 12 months
Confirmed Objective Response Rate (ORR) Assessed By Investigators
Time frame: From fist administration to the date that the last patients observed for 12 months
Time to Response (TTR) Assessed By independent radiology
Time frame: From fist administration to the date that the last patients observed for 12 months
Time to Response (TTR) Assessed By Investigators
Time frame: From fist administration to the date that the last patients observed for 12 months
Duration of response (DOR) Assessed By independent radiology
Time frame: From fist administration to the date that the last patients observed for 12 months
Duration of response (DOR) Assessed By Investigators
Time frame: From fist administration to the date that the last patients observed for 12 months
CNS response rate based on independent radiology review
Time frame: From fist administration to the date that the last patients observed for 12 months
CNS response rate based on investigator assessment
Time frame: From fist administration to the date that the last patients observed for 12 months
Time to CNS progression
Time frame: From fist administration to the date that the last patients observed for 12 months
Percentage of patients with adverse events
Time frame: 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)
Time frame: 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)
Time frame: From fist administration to the date that the last patients observed for 12 months
Patient reported time to deterioration (TTD)
Time frame: From fist administration to the date that the last patients observed for 12 months
Patient reported health-related quality of life (HRQoL)
Time frame: From fist administration to the date that the last patients observed for 12 months
Patient reported health-related quality of life (HRQoL)
Time frame: From fist administration to the date that the last patients observed for 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Derived from this study: PubMed 38280448Shi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing WX-0593 Tablets and crizotinib in people with Non-small Cell Lung Cancer, run by Qilu Pharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: from randomization until firstly recorded disease progression or death (whichever occurs earlier), or to the date that the last patients observed for 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04632758, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.