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

Inclusion Criteria: 1. 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: 2. 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: 1. Objective radiographic progression; OR 2. 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. Note for Cohorts A-2, Combination Dose-Selection, and Combination Expansion Phases: * 2 prior endocrine therapy regimens for recurrent/metastatic disease (adjuvant endocrine therapy leading to recurrence within 1 month of completion counts as 1 regimen). * 1 prior chemotherapy or ADC regimen for recurrent/metastatic disease. Prior CDK4/6 inhibitor use: 1. Duration ≥6 months; 2. Adjuvant CDK4/6 inhibitor use with progression \>1 year after completion does not count as resistance; 3. Switching CDK4/6 inhibitors due to intolerance is permitted. 3. For female patients in Combination Phases: Meet ≥1 of the following: 1. Bilateral oophorectomy; 2. Age ≥60 years; 3. Age \<60 years with natural menopause ≥12 months (without chemotherapy, tamoxifen, toremifene, or ovarian suppression in the past year), confirmed by postmenopausal FSH and estradiol levels; 4. Age \<60 years on tamoxifen/toremifene with postmenopausal FSH and estradiol levels. Non-postmenopausal patients must use LHRH agonists/antagonists throughout the study. 4. Baseline Lesions: Monotherapy dose-escalation: Extracranial evaluable/measurable lesions. Combination phases: Extracranial measurable lesions (RECIST 1.1). 5. ECOG performance status 0-1, no deterioration within 2 weeks prior to first dose (Appendix II). 6. Life expectancy ≥3 months. 7. Adequate Organ Function: Liver:TBIL ≤1.5×ULN, ALT/AST ≤2.5×ULN (≤5×ULN for liver metastases; ≤3×ULN for combination with fulvestrant). Kidney:Serum creatinine ≤1.5×ULN, creatinine clearance ≥50 mL/min (Cockcroft-Gault formula, Appendix III). Hematology:Platelets ≥90×10\^9/L, ANC ≥1.5×10\^9/L, Hb ≥90 g/L (without transfusion/G-CSF within 2 weeks). Cardiac:LVEF ≥50% (echocardiogram), QTcF \<470 ms. Coagulation:INR ≤1.5, APTT ≤1.5×ULN (without anticoagulation). 8. Contraception:Females of childbearing potential: Negative pregnancy test and commitment to highly effective contraception/abstinence from screening until 6 months post-treatment (Appendix IV).Males: Commitment to contraception/abstinence during the same period.For fulvestrant combination: Contraception until 1 year after last dose. 9. Voluntary signed ICF (or by legal guardian) and willingness to comply with study procedures. Exclusion Criteria: 1. Known hypersensitivity to any excipient of TYK-00540 or contraindication to fulvestrant (for Combination Dose-Selection and Combination Expansion Phases). 2. 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. 3. 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. 4. Residual toxicity from prior therapy \>G