A Phase III Study of SKB264 for EGFR Mutant NSCLC Patients

This is a randomized, open-label, multicenter Phase 3 clinical study to evaluate SKB264 monotherapy versus pemetrexed in combination with platinum in subjects with locally advanced or metastatic non-squamous NSCLC with EGFR mutation who have failed to EGFR-TKI therapy. The primary objective is to compare the efficacy and safety of SKB264 monotherapy versus pemetrexed in combination with platinum in patients with locally advanced or metastatic non-squamous NSCLC with EGFR mutation who have failed to EGFR-TKI therapy.

Inclusion criteria

• Males or females aged ≥18 to ≤75 years at the time of signing the ICF;
• Histologically or cytologically confirmed non-squamous NSCLC and locally advanced (stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC not amenable to radical surgery and/or radical concurrent/sequential chemoradiotherapy;
• EGFR-sensitive mutations;
• Failure of prior EGFR-TKI therapy;
• At least one measurable target lesion per RECIST 1.1 as assessed by the investigator;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Expected survival ≥12 weeks;
• Adequate organ and bone marrow function;
• Female subjects of childbearing potential and male subjects with partners of childbearing potential who use effective medical contraception from the time of signing the informed consent form until 6 months after the last dose;
• Subjects voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol-specified visits and relevant procedures

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%;
• Other malignancies within 3 years prior to the first dose;
• History of (noninfectious) interstitial lung disease (ILD)/noninfectious pneumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis;
• Subjects with active chronic inflammatory bowel disease, GI tract obstruction, severe ulcers, perforation gastrointestinal, abdominal abscess, or acute GI tract bleed;
• Toxicities from prior anti-tumor therapy not recovering to ≤ Grade 1 (per NCI CTCAE 5.0) or to the level specified in the eligibility criteria;
• Subjects with human immunodeficiency virus (HIV) test positive or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
• Prior TROP2-targeted therapy;
• Prior treatment with any drug therapy targeting topoisomerase I inhibitor, including antibody-drug conjugates (ADCs);
• Major surgery within 4 weeks prior to the first dose or expected to require major surgery during the study;
• Subjects who have received live vaccines within 30 days prior to the first dose, or are scheduled to receive live vaccines during the study;
• Pregnant or lactating women;