Phase 3 Clinical Study of AK112 for NSCLC Patients

The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare AK112 Plus Pemetrexed and Carboplatin to Placebo Plus Pemetrexed and Carboplatin in Patients with Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring. Approximately 320 subjects will be randomized to the two treatment at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of the AK112/Placebo Plus Pemetrexed and Carboplatin （Q3W,up to 4 cycles）in treatment periods per the randomization schedule. Afterward, AK112/ Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Inclusion criteria

• Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
• Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
• Life expectancy ≥3 months；
• Locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology, inoperable and unable to receive radiotherapy and chemotherapy;
• The tumor histology, cytology or hematology confirmed the presence of EGFR activating mutations before enrollment
• Have previously received EGFR-TKI treatment and the treatment has failed
• Subjects have at least one measurable non-brain tumor lesion per RECIST v1.1
• Major organ function prior to treatment meets the following criteria
• Patients of childbearing potential must agree to use effective contraceptive measures

Exclusion criteria

• Histological or cytological pathology confirmed the presence of small cell carcinoma components, or the main component is squamous cell carcinoma
• There are reports confirming the existence of other driver gene mutations with known drug treatments
• Subjects who received any prior treatments targeting the mechanism of tumor immunity
• The subject has received systemic anti-tumor therapy other than EGFR-TKI
• Currently enrolled in any other clinical study
• Received EGFR-TKI treatment, palliative local treatment, non-specific immunomodulatory treatment within 2 weeks prior to the first dose; and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 1 weeks prior to the first dose.
• Tumor surrounds important blood vessels or has obvious necrosis, cavitation, or invades surrounding important organs and blood vessels.
• Symptomatic central nervous system metastases
• Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors
• Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment
• There is a history of major diseases 1 year prior to the first dose.
• .Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose
• Received chest radiation therapy prior to the first dose
• Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
• Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).