This is a 2-part, phase I/II, open-label, multicenter study designed to evaluate the safety, PK, PD and preliminary efficacy of TCC1727 tablets administered orally QD.
Male or female subjects who have provided voluntary informed consent for participation in the study and to follow the protocol requirements
Male or female subjects 18-70 years of age
Subjects with histologically or cytologically confirmed malignant advanced solid tumors who have progressed on (or have not been able to tolerate) standard therapy or for whom no suitable effective standard therapy exists
For Phase I, all tumor types will be enrolled
Imaging examination suggests intracranial metastasis, which requires local treatment (in case of asymptomatic or symptomatic brain metastasis requiring no local treatment based on the investigator's judgement, the subject can still be included), or currently taking steroid hormone prior to inclusion, such as >10 mg prednisone (or equivalent) for intracerebral edema from brain metastases; subjects with meningeal carcinomatosis will be excluded regardless of their clinical stability
History of previously received major surgery or surgical therapy for any cause within 4 weeks of the first dose; radiotherapy, chemotherapy, other clinical trial drugs or other anti-tumor treatment, within 5 half-lives or 3 weeks (whichever is shorter), prior administering the first dose of study drug on Day 1
History of previous treatment with ATR inhibitors or other DDR related inhibitors (except poly ADP ribose polymerase enzyme (PARP) inhibitors)
carcinomas in situ, (e.g., breast, cervix, and prostate)
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Treatment groupsSee each treatment group below.