A Phase II Study of SKB264 + SKB118 in Nsq-NSCLC After EGFR-TKI Failure

Prior treatment

• Presence of known driver gene alterations with approved targeted therapies.
• Participants with other malignant tumors within 3 years prior to the first dose.
• Previous or concurrent gastrointestinal diseases, surgery, and wound healing complications.
• Unresolved toxicity from prior anti-tumor therapy, defined as toxicity not recovered to Grade 0 or 1 of CTCAE v6.0, or to the level specified in the inclusion/exclusion criteria, with the exception of alopecia.
• Serious infection within 4 weeks before the first dose, active infection requiring systemic anti-infective therapy within 2 weeks before the first dose.
• Participants who have received any of the following systemic anti-tumor therapies (including in the adjuvant or neoadjuvant setting):
  • Prior treatment with immune checkpoint inhibitors, immune checkpoint agonists, or any therapy targeting the immune mechanism of the tumor, such as immune cell therapy.
  • Prior treatment with PD-(L)1/VEGF bispecific antibodies or therapies targeting VEGF/VEGFR with monoclonal antibodies or small molecules.
  • Therapy targeting TROP2.
  • Any drug therapy targeting topoisomerase I, including antibody-drug conjugate (ADC) therapy.

Other illness

• Histologically or cytologically confirmed small cell lung cancer, neuroendocrine carcinoma, or sarcomatoid carcinoma components, or with a squamous component of more than 10%.
• History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid therapy, current ILD or non-infectious pneumonia.
• Presence of other moderate to severe lung disorders that may interfere with the detection or management of drug-related pulmonary toxicity and severely affect respiratory function.
• Risk of developing esophago-tracheal fistula or esophago-pleural fistula, or tumor invasion or compression of surrounding vital organs and major blood vessels.
• History of hemorrhagic diathesis or coagulopathy and/or clinically significant bleeding symptoms or risks.
• Presence of active hepatitis B or hepatitis C or co-infection with HBV and HCV.
• Positive human immunodeficiency virus (HIV) test or known history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
• Known active tuberculosis.
• Known history of allogeneic organ transplant or hematopoietic stem cell transplant.
• Active autoimmune disease requiring systemic treatment within the past two years.

Other

• Participants with known metastases to meninges, brainstem metastases, spinal cord metastases and/or compression, active or untreated brain metastases.
• Presence of uncontrolled, or symptomatic, or recurrent pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• With Grade ≥ 2 peripheral neuropathy.
• Pregnant or lactating women.

• Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC that is not suitable for radical surgery and/or radical radiotherapy (regardless of whether concurrent chemotherapy has been received).
• Confirmed EGFR-sensitizing mutations.
• Participants must have failed prior EGFR-TKI therapy for locally advanced or metastatic disease.
• Participants must be confirmed during the screening period to be able to provide a tumor tissue sample. If this cannot be met, acceptability should be discussed with the medical monitor.
• At least one measurable lesion as assessed by the investigator according to RECIST v1.1.
• ECOG performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Adequate bone marrow, liver, kidney, and coagulation function.
• Male and female participants must agree to use highly effective contraceptive measures during the specified period of the study.