A Phase I of FXS0260 in Advanced Solid Tumor

Inclusion Criteria:

1. Male or female participants aged ≥18 years;

2. Fully understand the requirements of this study and voluntarily sign the written informed consent form;

3. Participants with histologically/cytologically diagnosed advanced solid tumors who have received standard treatment before participating in this study and for whom standard treatment has failed or no standard treatment is available; priority will be given to participants with advanced endometrial cancer, advanced ovarian cancer, advanced colorectal cancer, advanced gastric cancer, and advanced breast cancer;

4. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 (lesions previously treated with radiotherapy cannot be considered target lesions unless obvious progression has occurred);

5. Eastern Cooperative Oncology Group performance status score of 0-1;

6. Life expectancy ≥12 weeks;

7. Adequate organ and bone marrow function:

   Hematology (no red blood cell or platelet transfusion or growth factor infusion within 7 days before the first administration of FXS0260):

   • Hemoglobin ≥95 g/L;
   • ANC ≥1.5 × 10⁹/L (≥1500 cells/mm³);
   • Platelet count ≥100 × 10⁹/L (≥100,000 cells/mm³);

   Coagulation:

   • Prothrombin time and APTT ≤1.5 × ULN;
   • INR ≤1.5 × ULN.

   Liver:

   • Total bilirubin ≤1.5 × ULN (if the participant is diagnosed with Gilbert's syndrome, total bilirubin ≤3 × ULN and direct bilirubin ≤1.5 × ULN are allowed);
   • ALT/AST ≤3 × ULN (≤5 × ULN in the presence of liver metastases).

   Kidney:

   • Creatinine clearance ≥60 mL/min. Creatinine clearance will be calculated using the Cockcroft-Gault formula.

8. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days before the first administration of the study drug; eligible participants of reproductive potential (male and female) must agree to use reliable contraceptive methods (hormonal or barrier methods or abstinence, etc.) together with their partners during the study and for at least 6 months after the last dose.

Exclusion Criteria:

1. Participants who are still within the washout period of previous antitumor treatment drugs before the first administration of FXS0260 (4 weeks or 5 half-lives after the last dose, whichever is shorter);

2. Participants who have previously received PKMYT1 inhibitors;

3. Participants who have participated in a clinical study within 4 weeks before the first administration of FXS0260;

4. Participants with a history of allergy to any known component or analogue of FXS0260;

5. Participants who require strong CYP3A inhibitors and/or inducers and P-gp inhibitors and/or inducers within 14 days (or 5 half-lives, whichever is longer) before the first administration and during the study;

6. Participants with active infections requiring systemic anti-infective treatment within 1 week before the first administration;

7. Participants who have received systemic glucocorticoids or other immunosuppressants, such as cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor α agents, within 14 days before the first administration;

8. Participants with other malignancies within 3 years before the first administration (except adequately treated basal cell/squamous cell carcinoma of the skin and carcinoma in situ of the cervix/breast);

9. Participants who have not recovered from adverse events caused by previous antitumor treatment (recovered to Grade 1 or baseline level), except for alopecia, pigmentation of any grade, peripheral sensory neuropathy of Grade ≤2, and items already explicitly specified in the inclusion criteria, as well as other abnormalities that are clinically insignificant or considered to pose no risk by the investigator;

10. Participants with a significant risk of thrombosis, such as deep vein thrombosis or pulmonary embolism within 3 months before screening, excluding venous thrombosis related to indwelling catheters or other procedures, superficial venous thrombosis, or thrombosis effectively treated with conventional anticoagulant therapy;

11. Participants with refractory nausea, vomiting, chronic gastrointestinal diseases including but not limited to active diverticulitis and symptomatic peptic ulcers, inability to swallow oral medications, or conditions such as previous extensive small bowel resection that, in the investigator's judgment, seriously affect gastrointestinal absorption;

12. Participants with a history of or current retinal vein stenosis or occlusion (RVO), retinal pigment epithelial detachment (RPED), central retinal vein occlusion, glaucoma, or other ocular diseases that affect the assessment of ocular toxicity after administration of the investigational product;

13. Participants who have undergone major surgery within 4 weeks before the first administration or have not recovered from surgical complications;

14. Participants who have received radiotherapy within 14 days before the first administration;

15. Participants with symptomatic or unstable brain metastases. Participants with previously treated brain metastases may participate in the study, provided that the following conditions are met: the metastatic lesions are stable (no evidence of progression on imaging examinations within 4 weeks before the first administration of study treatment, and any neurological symptoms are controlled and stable), there is no evidence of new or enlarging brain metastases, the investigator assesses the clinical condition as stable, and steroids have been discontinued for at least 14 days before the first administration of study treatment;

16. Participants with any of the following cardiovascular diseases:

    • Symptomatic heart failure (New York Heart Association [NYHA] functional classification ≥ Class II);
    • Left ventricular ejection fraction <50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan;
    • Poorly controlled hypertension repeatedly observed despite standard of care (SOC) treatment (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg);
    • Prolonged QT/QTc interval on electrocardiogram during screening (QTcF >470 ms);
    • Acute coronary syndrome/acute myocardial infarction, unstable angina, percutaneous coronary intervention or coronary artery bypass grafting within 6 months before screening;
    • Cardiomyopathy of any etiology or clinically significant valvular heart disease;
    • Transient ischemic attack or stroke within 6 months before screening that, in the investigator's judgment, may affect this study;
    • Severe arrhythmias requiring clinical intervention;
    • Any other cardiovascular disease that, in the investigator's opinion, makes the participant unsuitable for participation in the study.

17. Participants with uncontrolled pleural effusion, pericardial effusion, or ascites, or pleural effusion, pericardial effusion, or ascites requiring repeated drainage and medical intervention;

18. Participants with any of the following viral infections at screening:

    • Active hepatitis B: HBV-DNA >500 IU/mL or 2000 copies/mL;
    • Active hepatitis C: positive HCV antibody and positive HCV-RNA;
    • Human immunodeficiency virus (HIV) infection: positive antibody test;
    • Active syphilis: positive Treponema pallidum antibody (such as TPHA or FTA-ABS) and positive titer test (such as RPR or VDRL).

19. Participants with a history of interstitial lung disease, drug-induced interstitial lung disease or radiation pneumonitis requiring steroid treatment, or clinically active interstitial lung disease;

20. Participants with known drug abuse or psychiatric disorders that would interfere with compliance with study requirements;

21. Participants who are pregnant or breastfeeding or intend to become pregnant during the study;

22. Participants who, in the investigator's opinion, have other factors that may affect the study results or interfere with their participation throughout the study, including previous or existing physical conditions, treatments, or laboratory abnormalities, unwillingness to comply with the study procedures, restrictions, and requirements, or other circumstances that make them unsuitable for enrollment.