A Single-arm, Open-label, Multicenter, Phase Ib/II Clinical Trial of CVL237 Tablets in Combination With Serplulimab Injection for the Treatment of Advanced Solid Tumors With PTEN Loss or Low Expression

Exclusion Criteria

• •1. Surgery or Trauma: Undergone major organ surgery or experienced significant trauma within 4 weeks before the first administration of the study drug, or requires elective surgery during the trial period; undergone core needle biopsy or other minor surgeries (excluding central venous catheterization or port-a-cath implantation) within 7 days before the first dose;
• •2. Insufficient Washout Period for Prior Anti-tumor Treatments;
• •3. Inability to Swallow, Chronic Diarrhea, or Bowel Obstruction: Presence of factors that may affect the intake and absorption of the study drug;
• •4. Unhealed Wounds or Interventions: Unhealed wounds, abdominal fistulas, gastrointestinal stent placement, or extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months before the first dose;
• •5. Uncontrolled Effusions: Presence of uncontrolled pleural effusion, ascites, or pericardial effusion;
• •6. Concurrent Use of Certain Medications: Currently using medications that are substrates of OATP1B1 and OATP1B3, CYP3A4/5 substrates, moderate or strong CYP3A4/5 inhibitors, or strong CYP3A4/5 inducers, and cannot discontinue or switch to alternative treatments before starting the study treatment;
• •7. Central Nervous System (CNS) Metastases or Meningitis: Participants with untreated or active CNS metastases (e.g., brain edema, requiring steroid intervention, or progressive brain metastases) and/or carcinomatous meningitis. However, participants with CNS metastases who have received adequate local treatment (surgery or radiotherapy) and have no progression on imaging at screening after completion of local treatment may be eligible. Participants must have stable neurological symptoms for at least 2 weeks before the first dose and not require corticosteroid treatment;
• •8. History of Severe Allergic Reactions: Known history of severe allergic reactions to multiple medications;
• •10. Active or Potentially Recurrent Autoimmune Diseases: Participants with any active or history of autoimmune diseases that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis), except for clinically stable autoimmune thyroid disease or Type I diabetes;
• •11. Systemic Corticosteroid or Immunosuppressive Therapy: Participants who received systemic corticosteroids (prednisone \> 10 mg/day or equivalent) or other immunosuppressive agents within 14 days before the first dose of study drug. Exceptions include: Use of topical, ocular, intra-articular, nasal, or inhaled corticosteroids; Short-term (≤7 days) use of corticosteroids (≤10 mg prednisone equivalent) for prophylaxis or treatment of non-autoimmune allergic conditions (e.g., preventing contrast agent allergy);
• •12. Interstitial Pneumonia or Severe Pulmonary Diseases: Known or suspected interstitial pneumonia; other severe pulmonary diseases significantly affecting respiratory function within 3 months before the first dose, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans; non-infectious pulmonary inflammation requiring steroid treatment;
• •13. Infectious Diseases: Positive HIV test; participants with active chronic hepatitis B or active hepatitis C. Carriers of hepatitis B virus, stable hepatitis B after treatment (HBV DNA copy number below the detection limit of the testing center or deemed stable by the investigator), and cured hepatitis C patients (HCV RNA test result below the detection limit of the testing center) may be eligible;
• •14. Unresolved Adverse Events from Prior Anti-tumor Treatment: Adverse events from prior anti-tumor treatment that have not resolved to ≤ Grade 1 (CTCAE 5.0), except for alopecia or other toxicities deemed non-threatening by the investigator;
• •15. Severe Infections: Severe infection within 4 weeks before starting study treatment, including but not limited to bacteremia; active infection within 2 weeks before starting treatment requiring intravenous antibiotics;
• •16. Active Tuberculosis: History or CT evidence of active pulmonary tuberculosis within 1 year before enrollment;
• •17. Serious Cardiovascular or Cerebrovascular Events: Acute coronary syndrome, congestive heart failure (NYHA functional class ≥ II), aortic dissection, cerebral hemorrhage, stroke, or deep vein thrombosis within 6 months before the first dose;
• •18. Vaccination: Received live or attenuated vaccines within 30 days before the first dose of study drug, or planned to receive live or attenuated vaccines during the trial;
• •19. Other Primary Malignancies: History of other primary malignancies within 5 years before the first dose, except for cured basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc;
• •20. History of Allogeneic Organ or Hematopoietic Stem Cell Transplantation: Known history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplantation；
• •21. Other Conditions Deemed Ineligible by the Investigator: Such as alcohol or drug abuse, history of significant neurological or psychiatric disorders (e.g., epilepsy, dementia), or poor compliance.