Comparing TY-9591 and Osimertinib for advanced lung cancer

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.

This study is testing if a new drug called TY-9591 works better than the standard treatment Osimertinib for adults with advanced lung cancer that has specific genetic changes.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 680 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: TYK Medicines, Inc (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation, Osimertinib
• Locations: 2 sites (Changsha, Hunan and 1 other locations)
• Trial ID: NCT05382728 on ClinicalTrials.gov

What this trial studies

This Phase III clinical trial evaluates the efficacy and safety of TY-9591 compared to Osimertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for EGFR activating mutations. The study is double-blind and randomized, meaning neither the participants nor the researchers know who receives which treatment. Eligible participants are treatment-naïve adults with measurable disease and specific health criteria. The goal is to determine if TY-9591 offers a better treatment option than the standard therapy with Osimertinib.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with treatment-naïve, EGFRm-positive, locally advanced or metastatic NSCLC.

Not a fit: Patients with prior systemic antitumor therapy for their NSCLC or those with significant health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with advanced NSCLC.

How similar studies have performed: Other studies have shown success with EGFR-targeted therapies, indicating potential for positive outcomes with this approach.

Eligibility criteria

Inclusion Criteria:

1. Male or female aged ≥18 years and \<80 years.
2. Locally advanced or metastatic NSCLC diagnosed by histology or cytology.
3. 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).
4. No prior systemic antitumor therapy for locally advanced or metastatic NSCLC.
5. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
6. 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.
7. Adequate bone marrow reserve function, and no liver, kidney and coagulation dysfunction.
8. 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.
9. 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.
10. Patients can understand and voluntarily sign the informed consent form.
11. Patient able to comply with study requirements.

Exclusion Criteria:

1. Any of the following treatment:

   1. Previous treatment with EGFR inhibitor;
   2. Previous treatment with Systematic antitumor therapy (including targeted therapy, biotherapy and immunodrug therapy, etc.)；
   3. 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;
   4. 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;
   5. Uncontrollable or poorly controlled pleural and abdominal effusion;
   6. Major surgery within 28 days of the first dose of study treatment;
   7. 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;
   8. 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;
   9. Participants in other clinical trials (other than non-interventional clinical trials) within 28 days prior to the first administration of the investigational drug.
2. Pathologically confirmed squamous cell carcinoma or squamous cell component predominance in NSCLC.
3. Symptomatic brain metastases or leptomeningeal metastases.
4. Patients have spinal cord compression caused by tumor.
5. Clinically severe gastrointestinal dysfunction may affect the ingestion, transport or absorption of the study drugs.
6. Cardiac function and disease are consistent with the following:

   1. Corrected QT interval(QTc)≥ 470 milliseconds from 3 times of electrocardiograms (ECGs);
   2. Any clinically important abnormalities in rhythm;
   3. Any factors that increase the risk of QTc prolongation;
   4. Left ventricular ejection fraction (LVEF) \<50%.
7. 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.
8. Previous history of interstitial lung disease(ILD), drug-induced ILD or radiation pneumonitis require steroid treatment, or any evidence of clinically active ILD diseases.
9. Previous allogeneic bone marrow transplant.
10. Pregnant or lactating women.
11. Any other disease or medical condition that is unstable or may affect the safety or study compliance.
12. Hypersensitivity to investigational drug or similar compounds or excipients.

Where this trial is running

Changsha, Hunan and 1 other locations

• Hunan Provincial Tumor Hospital — Changsha, Hunan, China (Recruiting)
• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Baohui Han, MD — Shanghai Chest Hospital
• Study coordinator: Baohui Han, MD

Conditions NSCLC; EGFR Activating Mutation