GenSci145 as Monotherapy or in Combination Therapy, in Participants With PIK3CA-mutated, Locally Advanced or Metastatic Solid Tumors.

Inclusion Criteria: I. General inclusion criteria for all participants 1. Participants should be able to understand and voluntarily sign a written ICF (before participating in any trial-related procedures of this study). 2. Participants are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other specified study procedures. 3. At the time of signing the ICF: aged between 18 and 75 years (inclusive). If the legal age of consent in the jurisdiction in which the study is taking place is \> 18 years, then the legal age of consent should be reached. 4. Central or local test results are required to confirm the presence of eligible PIK3CA mutations in tumor tissue or blood samples. Eligible PIK3CA mutations include: R88Q, G106A/D/R/S/V, K111N/R/E, G118D, N345D/H/I/K/S/T/Y, C420R, E453A/D/G/K/Q/V, E542A/D/G/K/Q/R/V, E545A/D/G/K/L/Q/R/V, Q546E/H/K/L/P/R, T1025A/I/S, M1043I/T/V, N1044H/I/K/S/T/Y, H1047D/I/L/N/P/Q/R/T/Y, G1049A/C/D/R/S, or other pathogenic PIK3CA mutations. 5. Fresh tumor tissue (preferred) or archived tumor tissue sections are required (participants planning to be enrolled in Part 1 Dose Level 1 or Dose Level 2 who cannot provide tumor samples or provide insufficient samples can be screened after communicating with the sponsor). 6. At least one measurable lesion as assessed according to RECIST v1.1. 7. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 (refer to Appendix 1 for details). 8. Life expectancy ≥ 3 months. 9. Has adequate hematologic and organ function within 7 days prior to the first dose of GenSci145 as follows: Hematology:Neutrophil count ≥ 1,500/µL (1.5 × 109/L);Hemoglobin ≥ 9 g/dL;Platelet count ≥ 100,000/µL (100 × 109/L); Liver function:Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) (TBIL ≤ 3 × ULN for patients with Gilbert's syndrome); AST and ALT ≤ 2.5 × ULN; for participants with documented liver metastases: AST and/or ALT ≤ 5.0 × ULN; Renal function:Creatinine clearance rate (CLcr) ≥ 60 mL/min (Calculated by using the Cockcroft-Gault formula, refer to Appendix 3 for details); Glucose metabolism:•Fasting blood glucose ≤ 140 mg/dL (7.7 mmol/L);HbA1c ≤ 7.0%;Fasting blood amylase ≤ 2.0 × ULN;Fasting blood lipase ≤ 1.0 × ULN; Coagulation function:•International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN, or PT within the therapeutic range of intended anticoagulant treatment if the participant is receiving anticoagulant therapy;Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN, or aPTT within the therapeutic range of intended anticoagulant treatment if the participant is receiving anticoagulant therapy; 10. Women of childbearing potential (WOCBP) must be willing to use adequate contraception from signing the ICF until at least 30 days after the last dose of study treatment (or extended to 2 years if in combination with fulvestrant in accordance with the local prescribing information) and have a negative serum human chorionic gonadotropin (HCG) test within 7 days prior to the first dose of GenSci145. 11. Men able to father a child must be willing to use adequate contraception from signing the ICF until at least 30 days after the last dose. II. Inclusion criteria only applicable to specific study part/cohort Part 1: 1. Participants with histologically or cytologically confirmed locally advanced or metastatic solid tumors; 2. Participants with progressive disease following standard of care, or for whom, in the opinion of the investigator, no effective standard treatment regimen is available. Part 2: 1. Female participants with histologically or cytologically confirmed HR+/HER2- locally advanced or metastatic breast cancer \[HR+ in this protocol is defined as estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (positive nuclear staining in ≥ 10% tumor cells); HER2- is defined as immunohistochemistry (IHC) 0, 1+, or IHC 2+ and in situ hybridization (ISH) negative\]; 2. Participants with progressive disease following standard of care, or for whom, in the opinion of the investigator, no effective standard treatment regimen is available. Part 3 (Doublet), Part 4 Cohort A: 1. Female participants with histologically or cytologically confirmed HR+/HER2- locally advanced or metastatic breast cancer; 2. Participants who meet any of the following: 1. Participants with progressive disease during (neo)adjuvant endocrine therapy or within 12 months after completing the therapy and have not received any endocrine therapy for metastatic disease; 2. Progressive disease more than 12 months after completing adjuvant endocrine therapy, followed by progression again after one line of endocrine therapy (for metastatic disease); 3. Newly diagnosed advanced breast cancer with disease progresses following first-line endocrine therapy; 3. Have received ≤ 1 line of chemotherapy or antibody-drug conjugate therapy in the advanced stage; 4. Prior use of CDK4/6 inhibitors that meets any of the following: 1. Received a CDK4/6 inhibitor in the advanced stage and experienced progressive disease while on treatment or used a CDK4/6 inhibitor in the (neo)adjuvant setting and experienced progressive disease while on treatment; or within 12 months after the end of treatment; 2. Discontinuation of treatment due to intolerance to adverse reactions (e.g., hyperglycemia, rash, etc.); 3. If no prior use of CDK4/6 inhibitors, a plausible explanation (e.g., drug unavailability) is required. Part 3 (Triplet), Part 4 Cohort C: 1. Female participants with histologically or cytologically confirmed HR+/HER2- locally advanced or metastatic breast cancer; 2. Progression while on or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen; if a CDK4/6 inhibitor is included in the (neo)adjuvant setting, the progression event must have occurred \> 12 months after completing (neo)adjuvant therapy with CDK4/6 inhibitors. Part 4 Cohort B: 1.