Study of TYK-00540 Tablets in Patients With Advanced Solid Tumors

Recruiting now · Phase 1/Phase 2

Conditions studied: HR-positive, HER2-negative Advanced Breast Cancer

In brief

This study is to evaluate the safety, pharmacokinetics, and preliminary antitumor activity of TYK-00540 as monotherapy or combined with fulvestrant in advanced solid tumors.

Key facts

Study ID

NCT06950086

Run by

TYK Medicines, Inc

People needed

180

Starts

2024-01-02

Expected to finish

2026-11-01

Last updated by the study team

2025-04-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥18 years, gender requirements:
• Monotherapy dose-escalation phase: No gender restriction.
• Combination dose-selection phase: No gender restriction.
• Monotherapy and combination expansion phases:
• Cohort A-1: Females only.
• Other cohorts: No gender restriction.
• Monotherapy Dose-Escalation Phase:
• Histologically or cytologically confirmed locally advanced/metastatic solid tumors with no standard treatment available, failure of/intolerance to standard treatment, or refusal of standard treatment.
• Monotherapy Dose-Expansion Phase:
• Cohort A-1: Histologically or cytologically confirmed advanced platinum-resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer:
• Platinum resistance defined as: Disease recurrence/progression <6 months after completion of prior platinum-based chemotherapy (≥4 cycles) or progression during initial/recurrent treatment.
• Disease recurrence/progression requires:
• Objective radiographic progression; OR
• Persistent CA125 elevation (confirmed after 1 week) with clinical symptoms or signs of progression.
• 3 prior lines of chemotherapy for recurrent/metastatic disease, with ≤1 systemic therapy after platinum resistance.
• Cohort A-2: HR+/HER2- advanced breast cancer with confirmed resistance to CDK4/6 inhibitors (≥1 documented instance).
• Combination Dose-Selection Phase:
• HR+/HER2- advanced breast cancer with confirmed resistance to CDK4/6 inhibitors (≥1 documented instance).
• Combination Dose-Expansion Phase:
• Cohort B-1: HR+/HER2- advanced breast cancer with prior endocrine therapy resistance and either:
• No prior CDK4/6 inhibitor treatment; OR
• CDK4/6 inhibitor-treated in the adjuvant setting with recurrence >1 year after completion (no confirmed resistance).
• Cohort B-2: HR+/HER2- advanced breast cancer with progression during/after endocrine + CDK4/6 inhibitor therapy:
• For adjuvant CDK4/6 inhibitor resistance: Recurrence during or ≤1 year after treatment;
• ≥1 documented CDK4/6 inhibitor resistance.

You may not qualify if…

• Known hypersensitivity to any excipient of TYK-00540 or contraindication to fulvestrant (for Combination Dose-Selection and Combination Expansion Phases).
• Prior/concurrent therapies:
• Systemic anticancer therapies within 28 days prior to first dose: chemotherapy, large-molecule targeted therapy, immunotherapy.
• Endocrine therapy, small-molecule targeted therapy, or fluorouracil-based oral agents within 14 days prior to first dose.
• Nitrosoureas or mitomycin within 6 weeks prior to first dose. Anticancer herbal medicine or traditional Chinese medicine within 7 days prior to first dose.
• Local radiotherapy (e.g., thoracic/rib) or palliative radiotherapy for bone metastases within 7 days prior to first dose.
• Major surgery (excluding minor procedures, e.g., appendectomy, tumor biopsy) within 4 weeks prior to first dose.
• Proton pump inhibitor (PPI) use within 7 days prior to first dose or during the study.
• Concurrent use of medications known to prolong QTc interval or induce torsades de pointes (Appendix V).
• Participation in other interventional clinical trials within 28 days prior to first dose (non-interventional trials excluded).
• Prior allogeneic bone marrow transplantation. For Combination Phases: prior use of fulvestrant, other SERDs, or SERCAs.
• History of other malignancies, except:Cured basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma, ductal carcinoma in situ of the breast, or malignancies with disease-free survival >3 years.
• Residual toxicity from prior therapy >Grade 1 (except alopecia or platinum-related neuropathy).
• Central nervous system (CNS) disease:Primary CNS tumors, CNS metastases with prior local treatment failure, or newly diagnosed CNS metastases.Exception: Asymptomatic, stable CNS metastases (no steroids/CNS-specific treatment ≥14 days, radiologically confirmed stability at screening).
• Spinal cord compression caused by tumor.
• Visceral crisis.
• Clinically uncontrolled pleural effusion, ascites, or pericardial effusion requiring repeated drainage/medical intervention (within 14 days prior to first dose).
• Clinically significant ECG abnormalities at baseline (e.g., QTc ≥470 ms, complete LBBB, acute/indeterminate-age myocardial infarction, ST-T changes suggesting ischemia, second-/third-degree AV block, severe bradycardia/tachycardia).
• Cardiovascular events within 6 months:Myocardial infarction, long QT syndrome, torsades de pointes, arrhythmias (sustained ventricular tachycardia/fibrillation), severe conduction defects (e.g., bifascicular block, third-degree AV block), unstable angina, coronary/peripheral bypass, symptomatic CHF (NYHA Class III/IV), stroke, TIA, symptomatic pulmonary embolism, or clinically significant thromboembolism.Persistent NCI CTCAE ≥Grade 2 arrhythmia, atrial fibrillation (asymptomatic atrial fibrillation ≥Grade 2).
• Exception: Patients with cardiac pacemakers/devices and QTcF >470 ms may be eligible after discussion with the medical monitor.
• Unstable or uncontrolled medical conditions affecting safety/compliance, including:Uncontrolled hypertension (systolic BP >160 mmHg and/or diastolic BP >100 mmHg).Uncontrolled diabetes, active bleeding, ocular disease, severe psychiatric/neurological/cardiovascular/respiratory disorders.
• Active/uncontrolled infections or immunodeficiencies:Active HBV (HBsAg-positive with HBV DNA ≥2000 copies/mL [or 500 IU/mL]).Active HCV (HCV antibody-positive with HCV RNA-positive).HIV-positive.Exception: Asymptomatic chronic HBV/HCV carriers.
• Lung disease:Radiation pneumonitis requiring steroids, interstitial lung disease (ILD)/pneumonitis (active or drug-induced), acute/progressive pulmonary fibrosis, or high-risk factors for ILD per investigator judgment.
• Clinically significant gastrointestinal disorders affecting drug absorption (e.g., dysphagia, uncontrolled vomiting, active ulcers, inflammatory bowel disease, chronic diarrhea, bowel obstruction, chronic PPI-dependent conditions).
• Hypercoagulability with thromboembolic events within 6 months (e.g., stroke, DVT, pulmonary embolism).

Where it is running

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (enrolling)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (enrolling)

Full record on ClinicalTrials.gov

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