NSCLCPhase 3NCT05382728
Phase III Study of TY-9591 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLETEO)
A Phase 3 study testing TY-9591 and Osimertinib in people with NSCLC and EGFR Activating Mutation, run by TYK Medicines, Inc at 2 sites in China.
Trial summary
To assess the efficacy and safety of TY-9591 versus Osimertinib in patients with locally advanced or Metastatic Non Small Cell Lung Cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- NSCLC, EGFR Activating Mutation
- What is being tested?
- TY-9591 and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 680 participants
- Where
- 2 sitesChina
- Study dates
- 8 Jun 2022to Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged ≥18 years and <80 years.
- Locally advanced or metastatic NSCLC diagnosed by histology or cytology.
- Presence of an activating EGFR-sensitive mutations (including exon 19 deletions, L858R, the above mentioned mutations alone or co-existed with other EGFR-mutated sites).
- No prior systemic antitumor therapy for locally advanced or metastatic NSCLC.
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
- The ECOG score is 0-1, and there is no deterioration 2 weeks before the study, and the expected survival is not less than 3 months.
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- Adequate bone marrow reserve function, and no liver, kidney and coagulation dysfunction.
- Male patients and female patients of reproductive age should take adequate contraceptive measures from signing informed consent to 3 months after the last study drug treatment; Women of childbearing age have negative pregnancy test results within 7 days of the first dose.
- Patients having recovered from all grade ≤ 1 toxicities related to previous anticancer therapies (CTCAE v 5.0) except for alopecia, platinum-therapy-related neuropathy (where ≤2 is allowed) before first dose of study treatment.
- Patients can understand and voluntarily sign the informed consent form.
- Patient able to comply with study requirements.
Who cannot join
- Any of the following treatment:
- Previous treatment with EGFR inhibitor;
- Previous treatment with Systematic antitumor therapy (including targeted therapy, biotherapy and immunodrug therapy, etc.)；
- Previous treatment with standard chemotherapy with 28 days before the first dose of the study drug, and traditional Chinese medicine antitumor therapy within 7 days before the first dose of the study drug;
- Receiving radiation to more than 30% of the bone marrow or with a wide field of radiation that had to be completed within 28 days of the first dose of study treatment; Radiotherapy with a limited field of radiation within 7 days of the first dose of study treatment or palliative radiation therapy for bone metastasis;
- Uncontrollable or poorly controlled pleural and abdominal effusion;
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- Major surgery within 28 days of the first dose of study treatment;
- Patients currently receiving (or at least within 14 days prior to receiving the first dose )medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 isoenzyme (CYP)3A4;
- Patients who are receiving and need to continue receiving medications during the study that are known to prolong the QTc interval or may cause tachycardia;
- Participants in other clinical trials (other than non-interventional clinical trials) within 28 days prior to the first administration of the investigational drug.
- Pathologically confirmed squamous cell carcinoma or squamous cell component predominance in NSCLC.
- Symptomatic brain metastases or leptomeningeal metastases.
- Patients have spinal cord compression caused by tumor.
- Clinically severe gastrointestinal dysfunction may affect the ingestion, transport or absorption of the study drugs.
- Cardiac function and disease are consistent with the following:
- Corrected QT interval(QTc)≥ 470 milliseconds from 3 times of electrocardiograms (ECGs);
- Any clinically important abnormalities in rhythm;
- Any factors that increase the risk of QTc prolongation;
- Left ventricular ejection fraction (LVEF) <50%.
- Active human immunodeficiency virus (HIV), syphilis, hepatitis c virus (HCV) or hepatitis b virus (HBV) infection, with the exception of asymptomatic chronic hepatitis b or hepatitis c carriers.
- Previous history of interstitial lung disease(ILD), drug-induced ILD or radiation pneumonitis require steroid treatment, or any evidence of clinically active ILD diseases.
- Previous allogeneic bone marrow transplant.
- Pregnant or lactating women.
- Any other disease or medical condition that is unstable or may affect the safety or study compliance.
- Hypersensitivity to investigational drug or similar compounds or excipients.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Hunan Provincial Tumor Hospital
Changsha, Hunan, 410013
Lin Wu, MD, +8613170419973, Wulin-calf@vip.163.com
- Recruiting
Shanghai Chest Hospital
Shanghai, Shanghai Municipality, 201203
Baohui Han, MD, 18930858216, 18930858216@163.com
About this study
Official title: A Phase III, Randomised, Double-blind, Multi-center Study to Assess the Efficacy and Safety of TY-9591 Tablets Versus Osimertinib as First Line Treatment in Patients With EGFR-sensitive Mutation, Locally Advanced or Metastatic Non Small Cell Lung Cancer.
To assess the efficacy and safety of TY-9591 versus Osimertinib in patients with locally advanced or Metastatic Non Small Cell Lung Cancer.
Read the detailed description
This is a Phase III, double-blind, randomised study assessing the efficacy and safety of TY-9591 versus Osimertinib in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
- Conditions
- NSCLC, EGFR Activating Mutation
- Being tested
- TY-9591, placebo Osimertinib, Osimertinib, placebo TY-9591
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TY-9591Drug
Also called TY-9591 Tablets
The dose of TY-9591 is 160 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment.
Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
placebo OsimertinibDrug
Also called placebo Tagrisso
The dose of placebo Osimertinib is 80 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment.
Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
OsimertinibDrug
Also called Tagrisso
The dose of Osimertinib is 80 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment.
Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
placebo TY-9591Drug
Also called placebo TY-9591 Tablets
The dose of placebo TY-9591 is 160 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment.
Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
| Study group | Role | What they receive |
|---|---|---|
| TY-9591+placebo Osimertinib | Experimental | TY-9591 (160mg orally, once daily) plus placebo Osimertinib (80mg orally, once daily), in accordance with the randomization schedule. Receives: Drug: TY-9591; Drug: placebo Osimertinib |
| Osimertinib+placebo TY-9591 | Active comparator | Osimertinib (80mg orally, once daily) plus placebo TY-9591 (160mg orally, once daily), in accordance with the randomization schedule. Receives: Drug: Osimertinib; Drug: placebo TY-9591 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression Free Survival (PFS)
PFS is defined as time from randomization until the date of first documented disease progression or death due to any cause
Measured: approximately 18 months
Secondary outcomes (14)
Objective Response Rate (ORR)
ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) during the study treatment
Measured: approximately 18 months
Intracranial Overall Response Rate (iORR)
iORR is defined as the proportion of patients with a best intracranial response of complete response (CR) or partial response (PR) during the study treatment
Measured: approximately 18 months
Intracranial Median Progression Free Survival (iPFS)
iPFS is defined as time from randomization until the date of first documented intracranial disease progression or death due to any cause
Measured: approximately 18 months
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response (PR or CR) until the date of first documented disease progression or death due to any cause during the study treatment
Measured: approximately 18 months
Disease Control Rate (DCR)
DCR is defined as the proportion of patients with a best overall response of complete response (CR) , partial response (PR) or Stable disease (SD) ≥6 weeks during the study treatment
Measured: approximately 18 months
Clinical Benefit Rate (CBR)
CBR is defined as the proportion of patients with a best overall response of complete response (CR) , partial response (PR) or Stable disease (SD) ≥24 weeks during the study treatment
Measured: approximately 18 months
Depth of Response (DepOR)
The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir compared to baseline, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs)
Measured: approximately 18 months
Time To Progress (TTP)
TTP is defined as the time from randomization until the date of first documented disease progression (excluding death)
Measured: approximately 18 months
Overall Survival (OS)
OS is defined as the time from randomization until death from any cause
Measured: From the date of first dose until the date of death from any cause or loss to follow-up, whichever comes first, assessed up to 100 months
Assessment of health-related quality of life (FACT-L)
Change in FACT-L scores relative to Baseline
Measured: approximately 18 months
Safety variables
Adverse events, clinical symptoms, vital signs, ECG's, clinical laboratory safety tests, ect.
Measured: Assessments performed throughout the study period
Plasma Concentrations of TY-9591
To characterise the pharmacokinetics (PK) of TY-9591
Measured: approximately 18 months
Plasma Concentrations of TY-9591-D1
To characterise the pharmacokinetics (PK) of TY-9591 metabolite D1
Measured: approximately 18 months
Plasma Concentrations of TY-9591-D2
To characterise the pharmacokinetics (PK) of TY-9591 metabolite D2
Measured: approximately 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2022
- Study start8 Jun 2022
- Primary completionMay 2025 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 680 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TYK Medicines, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Baohui Han, MD, Principal investigator, Shanghai Chest HospitalLin Wu, MD, Principal investigator, Hunan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05382728
- Sponsor's protocol ID
- TYKM1601301
- Status last verified
- Jan 2024
- First submitted
- 16 May 2022
- Last updated
- 30 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomised, Double-blind, Multi-center Study to Assess the Efficacy and Safety of TY-9591 Tablets Versus Osimertinib as First Line Treatment in Patients With EGFR-sensitive Mutation, Locally Advanced or Metastatic Non Small Cell Lung Cancer.
- ClinicalTrials.gov ID
- NCT05382728
- Acronym / sponsor ID
- TYKM1601301
- Conditions
- NSCLC, EGFR Activating Mutation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 680 participants (estimated)
- Lead sponsor
- TYK Medicines, IncIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2022 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 19 May 2022 (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.
To assess the efficacy and safety of TY-9591 versus Osimertinib in patients with locally advanced or Metastatic Non Small Cell Lung Cancer.
Detailed description
This is a Phase III, double-blind, randomised study assessing the efficacy and safety of TY-9591 versus Osimertinib in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TY-9591+placebo Osimertinib | Experimental | Drug: TY-9591, Drug: placebo OsimertinibTY-9591 (160mg orally, once daily) plus placebo Osimertinib (80mg orally, once daily), in accordance with the randomization schedule. |
| Osimertinib+placebo TY-9591 | Active comparator | Drug: Osimertinib, Drug: placebo TY-9591Osimertinib (80mg orally, once daily) plus placebo TY-9591 (160mg orally, once daily), in accordance with the randomization schedule. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female aged ≥18 years and <80 years.
- Locally advanced or metastatic NSCLC diagnosed by histology or cytology.
- Presence of an activating EGFR-sensitive mutations (including exon 19 deletions, L858R, the above mentioned mutations alone or co-existed with other EGFR-mutated sites).
- No prior systemic antitumor therapy for locally advanced or metastatic NSCLC.
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Key exclusion criteria (25 listed)
- Any of the following treatment:
- Pathologically confirmed squamous cell carcinoma or squamous cell component predominance in NSCLC.
- Symptomatic brain metastases or leptomeningeal metastases.
- Patients have spinal cord compression caused by tumor.
- Clinically severe gastrointestinal dysfunction may affect the ingestion, transport or absorption of the study drugs.
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 |
|---|---|---|
| TY-9591Also: TY-9591 TabletsThe dose of TY-9591 is 160 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. | Drug | TY-9591+placebo Osimertinib |
| placebo OsimertinibAlso: placebo TagrissoThe dose of placebo Osimertinib is 80 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. | Drug | TY-9591+placebo Osimertinib |
| OsimertinibAlso: TagrissoThe dose of Osimertinib is 80 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. | Drug | Osimertinib+placebo TY-9591 |
| placebo TY-9591Also: placebo TY-9591 TabletsThe dose of placebo TY-9591 is 160 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. | Drug | Osimertinib+placebo TY-9591 |
Primary outcome
Median Progression Free Survival (PFS)
Time frame: approximately 18 months
PFS is defined as time from randomization until the date of first documented disease progression or death due to any cause
14 secondary outcomes
Objective Response Rate (ORR)
Time frame: approximately 18 months
Intracranial Overall Response Rate (iORR)
Time frame: approximately 18 months
Intracranial Median Progression Free Survival (iPFS)
Time frame: approximately 18 months
Duration of Response (DoR)
Time frame: approximately 18 months
Disease Control Rate (DCR)
Time frame: approximately 18 months
Clinical Benefit Rate (CBR)
Time frame: approximately 18 months
Depth of Response (DepOR)
Time frame: approximately 18 months
Time To Progress (TTP)
Time frame: approximately 18 months
Overall Survival (OS)
Time frame: From the date of first dose until the date of death from any cause or loss to follow-up, whichever comes first, assessed up to 100 months
Assessment of health-related quality of life (FACT-L)
Time frame: approximately 18 months
Safety variables
Time frame: Assessments performed throughout the study period
Plasma Concentrations of TY-9591
Time frame: approximately 18 months
Plasma Concentrations of TY-9591-D1
Time frame: approximately 18 months
Plasma Concentrations of TY-9591-D2
Time frame: approximately 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
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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.
Baohui Han, MD principal investigator
Shanghai Chest Hospital
Lin Wu, MD principal investigator
Hunan Cancer Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TY-9591 and Osimertinib in people with NSCLC and EGFR Activating Mutation, run by TYK Medicines, Inc at 2 sites 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 11 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Baohui Han, MD (18930858216, 18930858216@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Progression Free Survival (PFS) (time frame: approximately 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jan 2024.