A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of HSK46256 in Patients With Advanced Solid Tumors

Inclusion criteria

• Age ≥18 years, voluntarily participate and provide signed informed consent,
• ECOG performance status 0-1 or KPS >60; estimated life expectancy ≥12 weeks,
• Histologically or cytologically confirmed locally advanced or metastatic solid tumors, failed prior standard therapy, intolerant to standard therapy, or no available standard therapy,
• Dose escalation: prior treatment with one line of non-selective PARP inhibitor allowed,
• Documented HRR gene mutation,
• Agree to provide tumor tissue and/or blood samples,
• Fertile participants must agree to use effective contraception during study and for 3 months after last dose; negative pregnancy test for females,

Exclusion criteria

• Other malignancies within past 2 years (except adequately treated basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma);
• Uncontrolled moderate to large pleural, pericardial, or peritoneal effusions;
• Prior anticancer therapy or concomitant use of CYP3A4 strong/moderate inhibitors/inducers within protocol-specified washout periods;
• Prior anticancer treatment toxicity not resolved to CTCAE ≤Grade 1 (except alopecia, skin toxicity);
• Any condition affecting drug swallowing or significantly impacting drug absorption/PK;
• Severe or uncontrolled cardiac disease (QTcF prolongation, significant arrhythmia, LVEF <50%, recent MI/heart failure);
• Arterial/venous thromboembolic events within 6 months deemed uncontrolled risk;
• Severe/uncontrolled diabetes, hypertension, active bleeding, epilepsy, COPD, interstitial lung disease, active systemic infection;
• Unstable systemic disease (severe hepatic/renal/metabolic disorders);
• Prior MDS or AML diagnosis, or history of hematopoietic stem cell transplantation;
• Major surgery or severe trauma within 4 weeks;
• HIV positive, active hepatitis B/C, or active syphilis;
• Known hypersensitivity to study drug or excipients;
• Participation in another interventional trial within 4 weeks;
• Pregnant or lactating women;