This is a Phase Ib/II clinical study. The Phase Ib dose-escalation study aims to evaluate and determine the recommended Phase II dose (RP2D) of TCC1727 in combination with benmelstobart /olaparib /topotecanfor patients with advanced solid tumors.
The Phase II expansion study will assess the efficacy and safety of TCC1727 combined with benmelstobart /olaparib/topotecanin selected advanced solid tumor indications.
The study pre-specifies three treatment combinations, with Combination 1 (TCC1727 + benmelstobart) being prioritized for initial evaluation. The decision to proceed with Combination 2 and Combination 3will be based on clinical data from Combination 1.
-Voluntarily participate in this study and sign the informed consent form.
At the time of signing the informed consent, subjects must be ≥18 years of age (inclusive).
Phase Ib :Subjects with advanced, recurrent, or refractory solid tumors, which may include (but are not limited to) the specific tumor types in Phase II.
At least one measurable lesion (per RECIST v1.1; lesions previously treated with local therapy may be considered target lesions if they show clear progression per RECIST v1.1).
Known primary central nervous system (CNS) tumors (including meningeal tumors); symptomatic brain metastases, spinal cord compression, carcinomatous meningitis, or uncontrolled CNS metastases. Exceptions: Subjects with completely resected and/or irradiated CNS metastases that are stable or improved for ≥4 weeks before screening (no evidence of brain edema and no need for corticosteroids or anticonvulsants). Asymptomatic brain metastases <1 cm in diameter without surrounding edema are also allowed.
Major surgery, radiotherapy, chemotherapy, or other investigational anti-tumor therapy completed <4 weeks before the first dose (exceptions: small-molecule anti-tumor therapy completed >5 half-lives or >10 days before the first dose, whichever is longer; palliative radiotherapy completed >2 weeks before the first dose).
Use of strong CYP3A4 inhibitors or inducers within 14 days before the first dose (e.g., rifampin, rifapentine, St. John's wort, carbamazepine, phenytoin, barbiturates, ketoconazole, itraconazole, clarithromycin, voriconazole, atazanavir, ritonavir, saquinavir, grapefruit juice).
Any unresolved ≥Grade 2 toxicity (per CTCAE v5.0) from prior anti-tumor therapy (except alopecia, pigmentation, or laboratory abnormalities meeting inclusion criteria).