A Study of SKB264 (MK-2870; Sac-TMT) for the Treatment of Participants With Advanced or Metastatic Non-small Cell Lung Cancer (SKB264-II-04) (MK-2870-003)

This is a multicenter, open-label study of SKB264 as combination therapy or monotherapy in subjects with NSCLC. Approximately 498 subjects will be enrolled in this study including around 88 subjects for the safety run-in period and 410 subjects for the expansion period.

Inclusion criteria

• Subjects must be at least 18 years of age on day of signing informed consent, regardless of gender;
• Subjects with histologically or cytologically confirmed locally advanced or metastatic NSCLC ;
• Subjects for NSCLC should be confirmed to be EGFR (Epidermal growth factor receptor) wild-type and ALK (Anaplastic lymphoma kinase) fusion gene negative; or confirmed to harbor EGFR mutation;
• Locally advanced or metastatic NSCLC subjects without actionable EGFR mutations and ALK fusion genes, no prior systemic treatment; subjects with EGFR mutation, no prior systemic treatment or failed prior EGFR-TKI (Tyrosine kinase inhibitor) treatment;
• Subjects are able to provide tumor blocks or slides before the first dose of study intervention;
• Subject must have at least one radiographically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria;
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1;
• Life expectancy at least 3 months for the subject;
• Adequate organ function;
• Subjects must have recovered from all toxicities led by prior treatment;
• Contraceptive methods used by male and female subjects must comply with contraceptive methods of local regulations for clinical study subjects;
• Subjects should voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol-specified visits and relevant procedures.

Exclusion criteria

• Subjects with mixed SCLC histopathological features;
• Subjects with a known history of prior malignancy;
• Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases;
• Subjects with ≥ Grade 2 peripheral neuropathy;
• Subjects who had arteriovenous thromboembolic events, tumor invasion/encasement of vital organs/vessels, risk of esophageal-tracheal/pleural fistula, or current superior vena cava syndrome;
• Subjects with active inflammatory bowel disease or previous clear history of inflammatory bowel disease;
• Subjects who suffer from cardiovascular diseases of clinical significance;
• Subjects with a history of interstitial lung disease (ILD)/non-infectious pneumonitis that required steroids;
• Subjects with uncontrolled systemic disease as judged by the Investigator;
• Subjects with active autoimmune disease that required systemic treatment in the past 2 years;
• Subjects with active hepatitis B or hepatitis C;
• Subjects with known history of Human Immunodeficiency Virus (HIV)
• Subjects with known active tuberculosis;
• Subjects with known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study;
• Subjects whose condition deteriorated rapidly, such as severe changes in performance status, during the screening process prior to the first dose of study intervention;
• Subjects with other circumstances that, in the opinion of the Investigator, are not appropriate for participation in this study.