Breast Cancer Clinical Trials

⁃ Male or female subjets ≥ 18 years old.

⁃ Phase I Dose-Escalation Part: Patients with histologically or cytologically confirmed, surgically unresectable, locally advanced or metastatic malignant solid tumors, who have experienced failure of standard therapy, or for whom no standard therapy exists, or who are intolerant to standard therapy. (Priority will be given to enrolling patients with breast, ovarian, prostate, or pancreatic cancer harboring homologous recombination deficiency (HRD)-related gene mutations such as BRCA1/2, PALB2, RAD51C/D).

‣ Phase I Dose Backfill Portion: Patients with HER2-negative breast cancer (BC), advanced epithelial ovarian cancer (OC)/fallopian tube cancer (FTC)/primary peritoneal cancer (PPC), or castration-resistant prostate cancer (CRPC), who have a documented pathogenic or likely pathogenic BRCA mutation (BRCAm, germline or somatic) as detected by a local or central laboratory, and who have experienced failure of at least one prior line of standard anticancer therapy (refer to the protocol section for the Phase II dose expansion for specific standard therapy requirements); Or patients with other tumor types harboring homologous recombination deficiency (HRD) related gene mutations (including but not limited to esophageal cancer, small cell lung cancer, or pancreatic cancer) who have experienced failure of at least one prior line of standard therapy.

‣ Phase II Dose Expansion Study: Allows prior treatment with a pan-PARP inhibitor (no more than 1 type). Specific requirements for each cohort are as follows:

‣ Cohort 1: Breast Cancer (BC):

⁃ Histologically or cytologically confirmed HER2-negative (HR+/HER2- or triple-negative) advanced or metastatic breast cancer.

⁃ Presence of a predicted loss-of-function BRCA1/2 mutation in germline or tumor tissue.

⁃ Received at least \> 1 line of systemic therapy for advanced disease (must have received at least one line of chemotherapy; if HR+, must have received endocrine therapy), with recent radiological confirmation of disease progression.

‣ Cohort 2: Ovarian Cancer (OC):

⁃ Histologically confirmed high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

⁃ Presence of a predicted loss-of-function BRCA1/2 mutation in germline or tumor tissue.

⁃ Received at least \> 1 line of systemic therapy for advanced disease (must have received at least one platinum-based chemotherapy regimen for advanced disease), with recent radiological confirmation of disease progression.

⁃ Subjects must have a response duration of ≥ 6 months after the last platinum-based chemotherapy (platinum-sensitive population).

‣ Cohort 3: Prostate Cancer (PC):

⁃ Histologically or cytologically confirmed prostatic adenocarcinoma, which has progressed to the castration-resistant stage.

⁃ Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analog or status post bilateral orchiectomy, with serum testosterone \< 50 ng/dL (\< 1.73 nmol/L) within 28 days prior to study enrollment. Patients receiving ADT at the time of enrollment should continue this therapy throughout the study period.

⁃ Presence of a predicted loss-of-function BRCA1/2 mutation in germline or tumor tissue.

⁃ Received at least \> 2 lines of systemic therapy for advanced disease (must have received a novel hormonal agent \[NHA\] and chemotherapy), with recent radiological confirmation of disease progression.

‣ Cohort 4:

‣ 1\) The aforementioned tumor types (from Cohorts 1-3) harboring HRRm (excluding BRCA mutations), or other tumor types harboring HRRm (including but not limited to esophageal cancer, small cell lung cancer, or pancreatic cancer, etc.), which have failed after first-line or later standard therapy.

‣ 3\. Presence of at least one measurable lesion according to RECIST v1.1. 4. For both Phase I backfill and Phase II expansion, patients must provide tumor tissue (archived specimen from within 12 months pre-ICF preferred; fresh biopsy if unavailable) and peripheral blood for BRCAm/HRRm testing. Provision of specimens is also encouraged for Phase I dose-escalation patients when feasible. Testing will be conducted at a Sponsor-designated central laboratory. The samples provided shall comply with the following requirements:

• Option 1 : 8-10 sections of surgically resected tumor tissue specimens, or 10-15 sections of core needle biopsy specimens; fine needle aspiration specimens are not acceptable; plus approximately 2 mL of peripheral blood.

• Option 2 : If tumor tissue samples cannot be provided, a peripheral blood sample of approximately 10 mL may be provided instead.

‣ Note:BRCAm/HRRm results must meet eligibility criteria. A prior positive local laboratory report is acceptable for enrollment without awaiting central lab results; the central report will serve for retrospective validation. If sample quantity is insufficient, Sponsor consultation is required for enrollment eligibility.

‣ 5\. ECOG Performance Status of 0-1. 6. Expected survival time ≥ 3 months. 7. Adequate organ function:

‣ a. Hematopoietic system (Has not received blood transfusion or hematopoietic growth factor therapy within 14 days): i. Platelet count ≥ 100 × 10\^9/L ii. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L iii. White blood cell count ≥ 3.0 × 10\^9/L iv. Hemoglobin ≥ 90 g/L b. Hepatic function: i. Total bilirubin ≤ 1.5 × ULN ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (in the absence of liver metastases) iii. ALT and AST ≤ 5.0 × ULN (In subjects with liver metastases) c. Renal function: i. Creatinine clearance (Ccr) \> 50 mL/min (calculated by the Cockcroft-Gault formula) d. Coagulation function: i. Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN ii. International normalized ratio (INR) ≤ 1.5 × ULN 8. Both PARPi-pretreated and PARPi-naive patients are eligible for enrollment. For PARPi-pretreated patients, they are allowed to have received a maximum of one prior line of PARPi-containing therapy (whether as monotherapy or as maintenance therapy).

‣ 9\. Women of childbearing potential (WOCBP) (defined as those not surgically sterile or from menarche until 1 year after menopause) must have a negative serum pregnancy test result within 7 days prior to the first dose of the IP. WOCBP must agree to practice abstinence or use highly effective contraceptive methods from the time of signing the informed consent form until 3 months after the last dose of the IP. Similarly, male subjects (including those post-vasectomy) must agree to use effective contraception or practice abstinence from the time of signing the informed consent until 3 months after the last dose of the IP, and must refrain from sperm donation during this period.

‣ 10\. The subject must provide informed consent for the study prior to any trial-related procedures and voluntarily sign the written informed consent form.