A Study of SKB264 in Combination With Osimertinib Versus Osimertinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutations, Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

This is a randomized, open-Label, multicenter, Phase 3 study to evaluate the efficacy and safety of SKB264 in combination with osimertinib versus osimertinib alone as first-line treatment for patients with EGFR mutations, locally advanced or metastatic non-squamous non-small cell lung cancer.

Inclusion criteria

• Aged ≥18 years to ≤75 years at the time of signing the informed consent form (ICF), regardless of gender.
• Histologically or cytologically confirmed non-squamous NSCLC that is locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC not eligible to radical surgery and/or radical radiotherapy.
• No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC.
• Histologically or cytologically confirmed EGFR-sensitive mutations.
• Tumor tissue samples obtained at or after the diagnosis of locally advanced or metastatic tumor are eligible.
• At least one target lesion assessed by the investigator based on RECIST v1.1.
• ECOG performance status score of 0 or 1 within 7 days prior to randomization.
• Life expectancy ≥ 12 weeks.
• Adequate organ and bone marrow function.

Exclusion criteria

• Histologically or cytologically confirmed presence of small cell lung cancer, neuroendocrine carcinoma, and carcinosarcoma components or squamous cell carcinoma components of more than 10%.
• Subjects who have received prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC.
• Subjects who have received any of the following therapies (including the adjuvant/neoadjuvant therapy):

• Targeted TROP2 therapy;
• Any drug therapy that targets topoisomerase I, including antibody-drug conjugates (ADCs).
• Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, active or central nervous system (CNS) metastase.
• Other malignancies within 3 years prior to randomization.
• Clinically significant abnormalities found on resting electrocardiogram (ECG)
• Presence of any of cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors.
• History of interstitial lung disease (ILD), drug-induced ILD, history of non-infectious pneumonitis requiring steroid treatment, current ILD or non-infectious pneumonitis.
• Clinically severe lung injuries caused by lung diseases.
• Unresolved toxicities from previous anti-tumor therapy to ≤ Grade 1 (based on NCI CTCAE v5.0) or the level specified in the inclusion and exclusion criteria.
• Subjects who have received systemic corticosteroids > 10 mg/day of prednisone or other immunosuppressive agents within 2 weeks prior to randomization.
• Known active pulmonary tuberculosis.
• Known history of allogeneic organ transplant and allogeneic hematopoietic stem cell transplant.
• Presence of active hepatitis B or hepatitis C.
• Positive result of human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
• Known allergy to osimertinib, SKB264 or any of their components (including but not limited to polysorbate-20), history of severe hypersensitivity to other biologics.
• Vaccination with live vaccines within 30 days prior to randomization, or planned vaccination with live vaccines during the study.
• Women who are pregnant or breastfeeding.
• Presence of local or systemic diseases caused by non-malignancies, or diseases or symptoms secondary to tumors.