NSCLCPhase 2NCT05146219
Study of TY-9591 in Patients With a Lung Cancer With Brain or Leptomeningeal Metastases With EGFR Mutation
A Phase 2 study testing TY-9591 Tablets in people with NSCLC and EGFR Activating Mutation, run by TYK Medicines, Inc at 1 site in China.
Trial summary
To evaluate the efficacy and safety of TY-9591 tablets in the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) patients with brain or leptomeningeal metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, EGFR Activating Mutation, Brain Metastases
- What is being tested?
- TY-9591 Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteChina
- Study dates
- 2 Apr 2022to 13 Nov 2024
- Phase
- Phase 2
- 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
- Patients diagnosed with non-small cell lung cancer (NSCLC) by histology or cytology, and with brain and leptomeningeal metastases. For LM patients, the diagnosis of leptomeningeal metastasis requires detection of cancer cell or EGFR mutation in the CSF.
- 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). A positive T790M mutation is required for patients who have progressed following prior 1/2 generation EGFR-TKI therapy.
- Stable brain/leptomeningeal metastases that do not require immediate or planned local treatment for it during the study period.
- Presence of intracranial and extracranial measurable lesions without local treatment at the same time.
- The ECOG score is 0-2 (including 0 and 2), and there is no deterioration 2 weeks before the study, and the expected survival is not less than 3 months.
- Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
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- Absolute neutrophil count ≥1.5×109/L and white blood cell count ≥3×109/L;
- Platelet count ≥100×109/L;
- Hemoglobin ≥90g/L;
- Serum creatinine ≤1.5× upper normal limit (ULN) and creatinine clearance ≥50 mL/min (calculated according to the Cockcroft and Gault formula);
- AST and ALT≤2.5×ULN if no confirmed liver metastasis; AST, ALT≤5×ULN if confirmed liver metastasis;
- Total bilirubin ≤1.5×ULN in the absence of proven liver metastasis; total bilirubin ≤3×ULN in patients with proven liver metastasis or Gilbert syndrome (hyperindirect bilirubinemia);
- International standardized ratio (INR) ≤1.5, and activated partial prothrombin time (APTT) ≤1.5×ULN.
- 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 3rd generation EGFR inhibitor (Osimertinib, Almonertinib, Furmonertinib, etc.);
- The time from the treatment of reversible EGFR-TKI (e.g., Gefitinib, Erlotinib, Icotinib) to the first administration of the drug in this study did not exceed 8 days or 5 half-lives (whichever is longer); the time from the treatment of irreversible EGFR-tkis (e.g., Afatinib, Dacomitinib, Neratinib, etc.) do not exceed 14 days or 5 half-lives (whichever is longer);
- Previous treatment with Systematic antitumor therapy, including standard chemotherapy, biotherapy and immunodrug therapy within 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;
- Previous treatment with whole brain radiotherapy (WBRT). Patients who have previously received stereotactic radiotherapy (SRT) or other CNS local treatments (such as intrathecal chemotherapy) can be enrolled if the time from the completion of treatment to the initial study medication is more than 2 weeks;
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- Uncontrollable pleural and abdominal effusion. For patients with pleural effusion, pleural effusion should be stabilized for 2 weeks prior to initial medication (diuretics, pleural effusion or pleural infusion are not allowed during this period);
- Major surgery within 4 weeks 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 leptomeningeal metastases (LM) who cannot be examined with enhanced MRI. Presence of leptomeningeal metastases only.
- Patients with CNS complications requiring emergency neurosurgical treatment (e.g. surgery, etc.). Patients with CNS symptoms should be controlled by glucocorticoids with an equivalent dose of more than 5mg dexamethasone 5 days prior to initial administration.
- 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 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 TY-9591 or similar compounds or excipients.
Trial locations and contacts
1 site in 1 country.
China1 site
National Cancer Center/Cancer Hospitial,Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100021
About this study
Official title: A Phase II, Open-label, Multi-center Study to Evaluate the Efficacy and Safety of TY-9591 Tablets in Patients With EGFR-Mutated Non-small Cell Lung Cancer With Brain or Leptomeningeal Metastases
To evaluate the efficacy and safety of TY-9591 tablets in the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) patients with brain or leptomeningeal metastases.
Read the detailed description
This is an open label, multi-center phase II study to evaluate the efficacy and safety in EGFR mutated NSCLC patients with brain or leptomeningeal metastases. The patients will be assigned to the appropriate treatment cohorts based on the criteria.
- Being tested
- TY-9591 Tablets
- Medical subject headings
- Brain Neoplasms, Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TY-9591 TabletsDrug
Also called TY-9591
TY-9591 Tablets 160mg/d
| Study group | Role | What they receive |
|---|---|---|
| TY-9591 Tablets | Experimental | TY-9591 Tablets 160mg/d Receives: Drug: TY-9591 Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 13 months.
Extracranial Overall Response Rate (eORR)
eORR is defined as the proportion of patients with a best extracranial response of complete response (CR) or partial response (PR) during the study treatment
Measured: 13 months.
Secondary outcomes (6)
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: 13 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: 13 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: 13 months.
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: 13 months.
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: 13 months.
Overall Survival (OS)
OS is defined as the time from the date of first dose of study treatment 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2021
- Study start2 Apr 2022
- Primary completion21 Mar 2024
- Study completion13 Nov 2024
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- TYK Medicines, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yuankai Shi, MD, Principal investigator, Cancer Institute/Hospital, Chinese Academic of Medical Sciences and Peking Union Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05146219
- Sponsor's protocol ID
- TYKM1601201
- Status last verified
- Dec 2024
- First submitted
- 10 Nov 2021
- Last updated
- 30 Dec 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label, Multi-center Study to Evaluate the Efficacy and Safety of TY-9591 Tablets in Patients With EGFR-Mutated Non-small Cell Lung Cancer With Brain or Leptomeningeal Metastases
- ClinicalTrials.gov ID
- NCT05146219
- Acronym / sponsor ID
- TYKM1601201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- TYK Medicines, IncIndustry (pharma, biotech, devices)
- Study start
- 2 Apr 2022 (actual)
- Primary completion
- 21 Mar 2024 (actual)
- Study completion
- 13 Nov 2024 (actual)
- First posted
- 6 Dec 2021 (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 evaluate the efficacy and safety of TY-9591 tablets in the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) patients with brain or leptomeningeal metastases.
Detailed description
This is an open label, multi-center phase II study to evaluate the efficacy and safety in EGFR mutated NSCLC patients with brain or leptomeningeal metastases. The patients will be assigned to the appropriate treatment cohorts based on the criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TY-9591 Tablets | Experimental | Drug: TY-9591 TabletsTY-9591 Tablets 160mg/d |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients diagnosed with non-small cell lung cancer (NSCLC) by histology or cytology, and with brain and leptomeningeal metastases. For LM patients, the diagnosis of leptomeningeal metastasis requires detection of cancer cell or EGFR mutation in the CSF.
- 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). A positive T790M mutation is required for patients who have progressed following prior 1/2 generation EGFR-TKI therapy.
- Stable brain/leptomeningeal metastases that do not require immediate or planned local treatment for it during the study period.
- Presence of intracranial and extracranial measurable lesions without local treatment at the same time.
- The ECOG score is 0-2 (including 0 and 2), and there is no deterioration 2 weeks before the study, and the expected survival is not less than 3 months.
Key exclusion criteria (26 listed)
- Any of the following treatment:
- Patients with leptomeningeal metastases (LM) who cannot be examined with enhanced MRI. Presence of leptomeningeal metastases only.
- Patients with CNS complications requiring emergency neurosurgical treatment (e.g. surgery, etc.). Patients with CNS symptoms should be controlled by glucocorticoids with an equivalent dose of more than 5mg dexamethasone 5 days prior to initial administration.
- 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-9591 TabletsAlso: TY-9591TY-9591 Tablets 160mg/d | Drug | TY-9591 Tablets |
Primary outcome
Intracranial Overall Response Rate (iORR)
Time frame: 13 months.
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
Extracranial Overall Response Rate (eORR)
Time frame: 13 months.
eORR is defined as the proportion of patients with a best extracranial response of complete response (CR) or partial response (PR) during the study treatment
6 secondary outcomes
Objective Response Rate (ORR)
Time frame: 13 months.
Disease Control Rate (DCR)
Time frame: 13 months.
Duration of Response (DoR)
Time frame: 13 months.
Median Progression Free Survival (PFS)
Time frame: 13 months.
Intracranial Median Progression Free Survival (iPFS)
Time frame: 13 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2024.
- Individual participant dataSharing planned: No
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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.
Yuankai Shi, MD principal investigator
Cancer Institute/Hospital, Chinese Academic of Medical Sciences and Peking Union Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TY-9591 Tablets 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 17 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: finished, as of the sponsor's last update on 30 Dec 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Intracranial Overall Response Rate (iORR) (time frame: 13 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?
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 Dec 2024.