Study on Ivonescimab with Dato-DXd or Osimertinib for Non-Small Cell Lung Cancer

Inclusion Criteria

• Must provide written informed consent.
• Have metastatic non-small cell lung cancer confirmed by biopsy.
• Have an EGFR mutation in the tumor or blood sample that is sensitive to osimertinib.
• Previously treated with 3rd-generation EGFR TKI therapy and platinum-based chemotherapy, or ineligible for platinum-based chemotherapy.
• Have at least one measurable tumor that has not been treated with radiation.
• Have a performance status score of 0 or 1, indicating full activity or some restriction in strenuous activities.
• Be 18 years or older.
• Must be able to swallow oral medications (for Study Cohort B only).
• Have adequate organ function, including:
  • Liver enzymes (AST, ALT) within specified limits.
  • Total bilirubin within specified limits.
  • Kidney function within specified limits.
  • Low levels of protein in urine.
  • Adequate blood cell counts, including neutrophils, hemoglobin, and platelets.
  • Normal blood clotting times unless on stable anticoagulation therapy.
• Female patients of childbearing age must have negative pregnancy tests and agree to use effective contraception during and after treatment.
• Male patients must agree to use barrier contraception during and after treatment.

Exclusion Criteria

• Have a specific type of lung cancer (EGFR exon 20 insertion) not sensitive to osimertinib (for Study Cohort B only).
• Pregnant or breastfeeding women.
• Participation in another clinical study with treatment within the last 4 weeks.
• Previous treatment with anti-PD-1 therapy or certain antibody drug conjugates (for Study Cohort A only).
• History of significant corneal disease (for Study Cohort A only).
• Poorly controlled high blood pressure.
• Recent major surgery or trauma.
• History of bleeding disorders or significant bleeding symptoms.
• Active or prior autoimmune or inflammatory disorders, with some exceptions.
• History of major heart diseases or other serious medical conditions.
• Imaging shows major blood vessel or organ invasion by the tumor.
• History of another primary cancer, with some exceptions.
• Symptomatic brain metastases or recent brain radiation.
• Recent live vaccine or severe infection.
• Pre-existing severe nerve damage.
• Uncontrolled fluid buildup around the lungs, heart, or abdomen.
• History of lung disease requiring steroids.
• Uncontrolled HIV infection.
• History of organ or stem cell transplantation.
• Active hepatitis B or C infection.
• Known allergy to study drugs.
• Any condition that may interfere with the study or increase medical risk.