TR115 in ARID1A-Mutated Advanced Solid Tumors

Korábbi kezelés

• Prior treatment with EZH2 or EZH1/2 inhibitors resulting in disease progression (intolerance permitted).
• Systemic corticosteroid therapy (>10 mg/day prednisone or equivalent) within 14 days prior to first dose, except for inhaled or topical use.
• Prior anti-tumor therapy-related adverse events not recovered to ≤Grade 1 (CTCAE v6.0), except alopecia or peripheral neuropathy Grade ≤2.
• Use of strong or moderate CYP3A4 inhibitors/inducers within 14 days prior to first dose.

Más betegség

• Inability to swallow oral medication or conditions significantly affecting drug absorption.
• Active infection requiring systemic therapy.
• Active hepatitis B or C requiring treatment, or HIV infection.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Significant cardiovascular disease (e.g., myocardial infarction within 6 months, NYHA Class III/IV heart failure, uncontrolled arrhythmia).
• Other primary malignancy within 5 years, except cured non-melanoma skin cancer, carcinoma in situ, or thyroid carcinoma.
• Any other condition that in the investigator's opinion makes the participant unsuitable for the study.

Egyéb

• Third-space fluid accumulation not controllable by drainage or other means.
• Known central nervous system (CNS) involvement.
• Tumor invasion or encasement of major vessels.
• Pregnancy, lactation, or positive pregnancy test.

• Able to understand and provide written informed consent.
• Age 18 to 70 years, inclusive.
• Histologically or cytologically confirmed advanced solid tumor with ARID1A mutation.
• Cohort 1: Platinum-resistant ovarian/fallopian tube/peritoneal clear cell carcinoma with disease progression after ≥1 prior platinum-based regimen. Cohort 2: Endometrial cancer with disease progression after ≥1 prior platinum-based regimen and prior immunotherapy failure or intolerance. Cohort 3: Other advanced solid tumors (including gastric cancer, urothelial carcinoma) with disease progression after ≥1 prior standard systemic therapy.
• ECOG performance status 0-1.
• Life expectancy ≥3 months.
• At least one measurable lesion per RECIST v1.1.
• Adequate organ function: ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥100 g/L (no growth factor or transfusion support within 14 days prior to first dose), TBIL ≤1.5×ULN, ALT/AST ≤2.5×ULN (≤5×ULN if liver metastasis), CrCl ≥50 mL/min, LVEF ≥50%, QTcF <450 ms (male) or <470 ms (female).
• Willing to provide archival or fresh tumor tissue for biomarker analysis.
• Male and female participants of childbearing potential must agree to use medically approved contraception during the study and for 6 months after the last dose.