A Phase l Study of By101921, an Oral PARP7 Inhibitor, in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Male or female patients ≥18 years and ≤75 years of age.

2. patients histologically or cytologically diagnosed advanced malignant solid tumorswho have failed, cannot tolerate, or refuse prior standard treatment regimens. Atleast 1 measurable lesion per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

3. Have a projected life expectancy of at least 3 months.

4. Eastern Cooperative Oncology Group Performance Status 0 or 1.

5. Adequate organ and bone marrow function. Laboratory tests that meet the followingcriteria within 7 days prior to the first dose of study treatment (without bloodtransfusion, erythropoietin, recombinant human thrombopoietin or colony stimulatingfactor therapy, renal replacement therapy, etc., within 28 days prior to thescreening examination): Routine blood test: Absolute neutrophil count (ANC) ≥ 1.5×109/L Platelets count (PLT) ≥ 100×109/LHemoglobin (Hb) ≥ 90 g/L Hepatic function: Total bilirubin (TBIL) ≤ 1.5×ULN Aspartate aminotransferase (AST) ≤ 2.5×ULN Alanineaminotransferase (ALT) ≤ 2.5×ULN ALT and AST ≤ 5×ULN and TBIL ≤ 3×ULN for patientswith primary liver cancer, liver metastases, or Gilbert 's syndrome. Renal function: Creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft-Gault formula). Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN

6. Females and males of childbearing potential must agree to use appropriate methods ofcontraception (hormonal/barrier method or abstinence) during the study and for 3months after the last dose. Female subjects of childbearing potential must have anegative serum pregnancy test within 7 days prior to administration.

7. Understand and be willing to sign written informed consent and be able to follow thestudy protocol for treatment, visits, and other study procedures.

Exclusion Criteria:

1. Previously treated with PARP-7 inhibitors.

2. Treated with a potent CYP3A4 inhibitor or inducer within 2 weeks prior to the firstdose of study treatment.

3. Previous any treatment with of the following:

4. Systemic chemotherapy, other antitumor agents (including endocrine therapy,macromolecular targeted therapy, immunotherapy, or biotherapy) within 4 weeksor 5 half-lives prior to the first dose of study treatment, or who need tocontinue receiving these agents during the study period;

5. Small molecule targeted therapy within 2 weeks or 5 half-lives prior to thefirst dose of study treatment;

6. Anti-tumor traditional Chinese medicine or proprietary Chinese medicinepreparations prior to the first dose of study treatment;

7. Nitrosourea or mitomycin C within 6 weeks prior to the first dose of studytreatment;

8. Palliative radiation therapy within 2 weeks prior to the first dose of studytreatment;

9. Investigational drug within 4 weeks prior to the first dose of study treatment;g Radical radiation therapy within 4 weeks prior to the first dose of studytreatment.

10. Major surgical intervention (excluding needle biopsy) within 28 days before studydrug administration, surgical wound has not fully healed or surgery is scheduledduring the study period.

11. Brain metastasis (except asymptomatic, stable for more than 4 weeks prior to thefirst dose and not requiring steroid therapy for at least 4 weeks prior to the firstdose, no imaging findings of marked edema around the tumor lesion), presence ofmeningeal metastasis or brainstem metastasis, or presence of spinal cordcompression.

12. History of other malignancy within the past 5 years, except skin basal cellcarcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, or othercarcinomas in situ which have undergone curative treatment and have had norecurrence within 5 years after treatment.

13. Toxicities from prior antitumor therapy that have not recovered to CTCAE version 5.0Grade 1 or less, except CTCAE (V5.0) Grade 2 peripheral neurotoxicity and alopeciaof any grade.

14. Difficult-to-control pleural effusion, ascites, or pericardial effusion.etc,requiring repeated drainage and considered unsuitable for study enrollment by theinvestigator.

15. Serious or uncontrolled diseases as assessed by the investigator, including but notlimited to: Severe or uncontrolled diabetes, poorly controlled hypertension (systolic bloodpressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg under standardizedantihypertensive regimens), epilepsy, chronic obstructive pulmonary disease,interstitial pneumonia, pulmonary interstitial fibrosis, Parkinson 's disease,active bleeding, uncontrolled infection. Cognitive dysfunction, history of psychiatric disorders, other uncontrolledconcomitant diseases, alcohol dependence, hormone dependence, or drug abuse. History of immunodeficiency, including HIV antibody positive, other acquired orcongenital immunodeficiency disease, or history of organ transplantation. HBsAg or HBcAb positive, and peripheral blood HBV DNA titer test ≥ 200 IU/mL or ≥ 1000 copies/mL or above the upper limit of normal value at the study site; HCVantibody test positive, and HCV RNA test above the upper limit of normal value atthe study site; treponema pallidum-specific antibody positive. Clinically serious gastrointestinal dysfunction that may compromise drug intake,transport, or absorption. For example, inability to take oral medication,uncontrollable nausea or vomiting, history of massive gastrointestinal resection,history of gastrointestinal ulcer and gastrointestinal bleeding within 6 monthsprior to the first dose, untreated recurrent diarrhea, untreated stomach diseaserequiring long-term use of PPI acid suppressants, Crohn 's disease, ulcerativecolitis, etc.

16. Cardiac dysfunction, including any of the following: Myocardial infarction in past 6 months, heart failure classified as Class II/III/IVaccording to the New York Heart Association (NYHA) Functional Classification,unstable angina pectoris, and unstable arrhythmia. Left ventricular ejection fraction LVEF < 50% shown by echocardiography. QT intervalcorrected using Fridericia 's formula: QTcF > 470 msec (females), QTcF > 450 msec (males).

17. Pregnant (positive pregnancy test prior to dosing) or lactating.

18. History of serious hypersensitivity (e.g., anaphylactic shock) or hypersensitivityto excipients or other ingredients associated with the study drug.

19. Cannot follow the protocol to "avoid ingesting grapefruit , pomegranate, orange orgreen lemon (juice/sauce made from these fruits as well) within 7 days before studydrug administration and throughout the BY101921 treatment period".

20. Other factors considered unsuitable for study enrollment by the investigator.