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NSCLCPhase 2NCT05948813

TY-9591 in the Patients With EGFR Mutations in Advanced NSCLC With Brain Metastases

A Phase 2 study testing TY-9591 and Osimertinib in people with NSCLC and EGFR Activating Mutation, run by TYK Medicines, Inc at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This study is to evaluate the efficacy and safety of TY-9591 in first-line treatment of patients with EGFR-sensitive mutation-positive non-small cell lung cancer with brain metastases compared to Osimertinib. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
NSCLC, EGFR Activating Mutation, Brain Metastases
What is being tested?
TY-9591 and Osimertinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
420 participants
Where
1 siteChina
Study dates
17 Aug 2023to 30 Mar 2030
Phase
Phase 2
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.
  • Patients diagnosed with NSCLC by histology or cytology, with brain metastases.
  • 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.
  • Stable brain metastases that do not require immediate or planned local treatment for it during the study period.
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
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  • 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.
  • 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;
  • Previous whole brain radiation therapy (WBRT); 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, abdominal and pericardial effusion;
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  • Uncontrollable cancerous pain; Anesthetic painkillers did not reach a stable dose at the time of enrollment;
  • 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.
  • Patients with primary malignant brain tumors and unstable brain metastases.
  • Patients who have had or have a history of other malignancies within the past 5 years (except cured basal cell or squamous cell carcinoma of the skin, papillary carcinoma of the thyroid gland, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast).
  • The patient had symptoms of spinal cord compression caused by the 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 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) or 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 TY-9591 or similar compounds or excipients.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yuankai Shi, MD contact

+86-10-87788293

syuankaipum@126.com

China1 site, 1 recruiting

  • National Cancer Center/Cancer Hospitial,Chinese Academy of Medical Sciences and Peking Union Medical College

    Beijing, Beijing Municipality, 100021

    Yuankai Shi, MD, +861087788293, syuankaipum@126.com

    Recruiting

Other trials in China

About this study

Official title: A Phase II Study of TY-9591 Tablets in Patients With EGFR-Mutated Non-small Cell Lung Cancer With Brain Metastases

This study is to evaluate the efficacy and safety of TY-9591 in first-line treatment of patients with EGFR-sensitive mutation-positive non-small cell lung cancer with brain metastases compared to Osimertinib.

Read the detailed description

This is an open label, multi-center phase II study to compare the efficacy and safety with Osimertinib in EGFR mutated NSCLC patients with brain metastases. Participants will be randomly assigned to one of the TY-9591 group (160mg orally, once daily) or Osimertinb group (80mg orally, once daily) . Participants can continue to receive study treatment as long as disease progression, meeting criteria for discontinuation of treatment, withdrawal criteria, or study termination (whichever occurred first).

Being tested
TY-9591, Osimertinib
Medical subject headings
Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TY-9591Drug

    The dose of TY-9591 tablet is 160 mg once daily. A cycle of treatment is defined as 21 days of once daily treatment until meet the 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 until meet the of discontinuation criteria.

Study groups in NCT05948813
Study groupRoleWhat they receive
TY-9591 TabletsExperimentalTY-9591 (160mg orally, once daily), in accordance with the randomization schedule.
Receives: Drug: TY-9591
OsimertinibActive comparatorOsimertinib (80mg orally, once daily), in accordance with the randomization schedule.
Receives: Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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: 36 months

  2. Intracranial Median Progression Free Survival (iPFS)

    iPFS is defined as time from date of first dose of study treatment until the date of first documented intracranial disease progression or death due to any cause

    Measured: 36 months

Secondary outcomes (14)

  1. 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: 36 months

  2. Median Progression Free Survival (PFS)

    PFS is defined as time from date of first dose of study treatment until the date of first documented disease progression or death due to any cause

    Measured: 36 months

  3. 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: 36 months

  4. Intracranial Disease Control Rate (iDCR)

    iDCR is defined as the proportion of patients with a best intracranial response of complete response (CR) , partial response (PR) or Stable disease (SD) ≥6 weeks during the study treatment

    Measured: 36 months

  5. Depth of Response (DepOR)

    The Depth of response was defined as the relative change in the sum of the longest diameters of Target lesions (TLs) at the nadir compared to baseline, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs)

    Measured: 36 months

  6. Intracranial Depth of Response (iDepOR)

    iDepOR was defined as the relative change in the sum of the longest diameters of intracranial Target lesions (TLs) at the nadir compared to baseline, in the absence of intracranial new lesions (NLs) or progression of intracranial Non-target lesions (NTLs)

    Measured: 36 months

  7. Intracranial Time to Response (iTTR)

    iTTR is defined as the time from randomization to the first assessment of CR or PR for intracranial tumors

    Measured: 36 months

  8. 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: 36 months

  9. Intracranial Duration of Response (iDoR)

    iDoR is defined as the time from the date of first documented intracranial response (PR or CR) until the date of first documented disease progression or death due to any cause during the study treatment

    Measured: 36 months

  10. Overall Survival (OS)

    OS is defined as the time from randomization until death from any cause

    Measured: Up to approximately 60 months

  11. Assessment of health-related quality of life (FACT-L)

    Change in FACT-L scores relative to Baseline

    Measured: 36 months

  12. Safety variables

    Adverse events, clinical symptoms, vital signs, ECG's, clinical laboratory safety tests, ect.

    Measured: Up to approximately 60 months

  13. Assessment of Karnofsky and NANO

    Change in Karnofsky and NANO scores relative to Baseline

    Measured: 36 months

  14. Plasma Concentrations of TY-9591 and metabolite

    To characterise the pharmacokinetics (PK) of TY-9591 and TY-9591 metabolite

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2023
  2. Study start17 Aug 2023
  3. Primary completion15 Dec 2025
  4. Study completion30 Mar 2030 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
420 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05948813
Sponsor's protocol ID
TYKM1601202
Status last verified
Aug 2026
First submitted
9 Jul 2023
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TY-9591 and Osimertinib in people with NSCLC and EGFR Activating Mutation, run by TYK Medicines, Inc 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 12 inclusion and 26 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 25 Aug 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Yuankai Shi, MD (+86-10-87788293, syuankaipum@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial Overall Response Rate (iORR) (time frame: 36 months). The study lists 2 primary outcomes in all. 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 NCT05948813.

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 25 Aug 2026.

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