A Study of XS-04 in Patients with Relapsed or Refractory Hematologic Malignancies

Exclusion Criteria

• •Burkitt lymphoma/leukemia, plasma cell myeloma, plasmablastic lymphoma.
• •Acute promyelocytic leukemia (APL) or BCR-ABL positive AML patients or those with a history of myeloproliferative neoplasms (MPN).
• •Use of other cytotoxic drugs, investigational drugs, or other antitumor drugs within 14 days or 5 half-lives before the first dose of the study drug (whichever is shorter) (except hydroxycarbamide and leukapheresis). Patients who received tumor immunotherapy, antibody, or peptide antitumor drug treatment within 4 weeks before the first dose of the study drug.
• •Patients who underwent therapeutic surgery other than diagnostic, biopsy, or drainage procedures within 4 weeks before the first dose of the study drug, or who are expected to undergo major surgery during the study. For patients who underwent drainage procedures (e.g., thoracic, biliary, etc.) and/or placement of drainage tubes within 4 weeks before the study drug, related symptoms/signs must have substantially resolved, and no prophylactic/therapeutic use of antibiotics is required.
• •Systemic radiotherapy within 4 weeks before the first dose of the study drug.
• •Unresolved toxic reactions from previous antitumor treatments (\> NCI-CTCAE 5.0 grade 1), alopecia, pigmentation, neurotoxicity, or other toxicities assessed by the investigator as chronic and not affecting the safety of the study drug, resolved to NCI-CTCAE 5.0 grade 2 or below are allowed for enrollment.
• •Previous allogeneic stem cell transplantation; autologous stem cell transplantation or adoptive immune cell therapy within 3 months before the first dose of the study drug (mature B-cell malignant tumor patients) or within 6 months (AML, MDS patients).
• •Patients with lymphoma/leukemia involving the central nervous system (CNS).
• •Dysphagia, or a history of severe gastrointestinal disease (e.g., active inflammatory bowel disease, gastrointestinal perforation) with symptoms that cannot be reasonably controlled; or gastrointestinal diseases affecting drug absorption (e.g., Crohn's disease, ulcerative colitis, ileus, short bowel syndrome) or other malabsorption conditions.
• •Patients with ocular conjunctival, corneal lesions (can be enrolled after treatment of ocular lesions is cured).
• •Patients with active or unstable cardiovascular and cerebrovascular diseases, including but not limited to:
• •1. Severe cardiac rhythm or conduction abnormalities requiring clinical intervention;
• •2. Acute coronary syndrome, congestive heart failure, myocardial infarction, unstable angina, coronary/peripheral artery bypass grafting, cerebral infarction, cerebral hemorrhage, pulmonary embolism, deep vein thrombosis (within 3 months before the first dose) or other severe cardiovascular events within 6 months before the first dose;
• •3. New York Heart Association (NYHA) heart function classification ≥II;
• •4. Left ventricular ejection fraction (LVEF) \<50%;
• •5. Presence of torsades de pointes, congenital long QT syndrome;
• •6. QTcF \>450ms (male) or \>470ms (female);
• •7. Uncontrolled hypertension despite optimal treatment (defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg under medication control).
• •History of interstitial lung disease (ILD), pulmonary interstitial fibrosis; or evidence of active pneumonia on chest CT scan during the screening period.
• •Patients with congenital immune deficiency diseases, or active autoimmune diseases, including but not limited to active and uncontrolled autoimmune cytopenia, persisting for 2 weeks or longer, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.
• •Patients with coagulopathy (e.g., hemophilia).
• •Currently using anticoagulant drugs.
• •History of severe allergies, or allergies to any active or inactive components of the study drug.
• •Uncontrolled systemic infection (viral, bacterial, fungal) within two weeks before the first dose of the study drug; hepatitis B surface antigen positive and hepatitis B virus DNA exceeding 1000 IU/ml; hepatitis C virus (HCV) antibody positive or HCV RNA positive; human immunodeficiency virus (HIV) antibody positive.
• •Patients with other primary malignant neoplasms, the following conditions can be enrolled: cured and completely excised basal cell and squamous cell skin cancer, completely excised carcinoma in situ of any type.
• •Need to continue using systemic immunosuppressants or systemic corticosteroids (≥10mg prednisone or equivalent of other corticosteroids) within two weeks before the study drug.
• •Use of strong CYP3A inhibitors or inducers within two weeks before the first dose.
• •Pregnant or lactating women.
• •Any other severe or uncontrolled acute or chronic disease or laboratory test abnormality or other reasons deemed unsuitable for participation in this clinical study by the investigator.