Phase III Study of AK112 for NSCLC Patients

Inclusion Criteria:

1. Ability to understand and voluntarily sign a written informed consent form (ICF),which must be signed before the specified study procedures required for the studyare performed.

2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent. (For patients from North America and Europe, there will be no upper age cutoff)

3. ECOG performance status score of 0 or 1.

4. Expected survival ≥3 months.

5. Histologically or cytology-confirmed, locally advanced (Stage IIIB/IIIC) ormetastatic (Stage IV) non-squamous NSCLC (according to TNM staging of lung cancer, 8th edition) that cannot be completely resected by surgery and cannot receiveradical concurrent/sequential chemoradiation.

6. EGFR activation mutations that are confirmed by tumor histology or cytology or bloodtest before enrollment (eg, exon 18 point mutations, exon 19 deletions, exon 20point mutations, and exon 21 point mutations). Patients must provide a previous EGFRmutation test report, otherwise tumor tissue samples, peripheral blood samples, orpleural fluid samples will need to be collected for EGFR status testing prior toenrollment.

7. Prior treatment with EGFR TKI and treatment failure, meeting any of the followingrequirements: Progression after treatment with first- or second-generation EGFR TKI,and confirmation of absence of T790M mutation after progression (only for patientsenrolled in China). Progression after treatment with a third-generation EGFR TKI (eg, osimertinib, ametinib, vometinib). Note, for North America and Europe patientsonly.

8. According to RECIST v1.1, there is at least 1 measurable noncerebral lesion.

9. Adequate organ function determined by the following requirements

10. Female patients of childbearing age have a negative serum pregnancy test resultwithin 3 days before the first dose

11. If a female patient of childbearing potential has sex with an unsterilized malepartner, the patient must use a highly effective method of contraception from thebeginning of screening and must agree to continue using these precautions until 120days after the last dose of the study drug or until 6 months after the lastcarboplatin and pemetrexed dose (whichever is longer).

12. If an unsterilized male patient has sex with a female partner of childbearingpotential, the patient must use an effective method of contraception from thebeginning of screening to day 120 after the last dose or until 6 months after thelast carboplatin and pemetrexed dose (whichever is longer). The decision to stopcontraception after this time point should be discussed with investigator.

Exclusion Criteria:

1. Histologic or cytopathologic evidence of the presence of a small cell carcinomacomponent, or a predominantly squamous cell carcinoma.

2. Patients who have received immune checkpoint inhibitors (eg, anti-PD-1/L1antibodies, anti-CTLA-4 antibodies, anti-LAG-3 antibodies, etc.)

3. Received prior systemic chemotherapy, anti-angiogenic therapy, or more than oneprior line of antitumor therapy (other than EGFR inhibitors) for advanced stage (IIIB to IV) NSCLC.

4. Concurrent enrollment in another clinical study, unless it is a noninterventionalclinical study or the follow-up period of the interventional study is more than 4weeks from the last dose of the prior clinical study or more than 5 half-lives ofthe prior study drug, whichever is shorter.

5. Received EGFR inhibitor therapy within 2 weeks (with the exception of osimertinib tobe within 7 days) prior to the first dose; received nonspecific immunomodulatorytherapy (eg, interleukin, interferon, thymus peptide, tumor necrosis factor) within 2 weeks prior to the first dose, excluding IL-11 for the treatment ofthrombocytopenia; have received Chinese herbal medicines or proprietary Chinesemedicines with antitumor indications within 1 week before the first dose.

6. Imaging during the screening period shows that the tumor surrounds important bloodvessels or has obvious necrosis and/or cavitation of tumor lesions within the lungparenchyma.

7. Imaging during the screening period shows that the tumor invades the surroundingvital organs and blood vessels, such as the heart and pericardium, trachea,esophagus, aorta, superior vena cava, or patient is at risk of esophageal trachealfistula or esophageal pleural fistula.

8. Symptomatic metastases of the central nervous system.

9. Malignant tumors other than NSCLC within 3 years before the first dose.

10. Active autoimmune disease requiring systemic therapy (eg, with disease-modifyingdrugs, corticosteroids, immunosuppressant therapy) within 2 years prior to the firstdose (excluding ir AEs due to PD-1/L1 inhibitors). Replacement therapy (eg,thyroxine, insulin, or physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent) for adrenal or pituitary insufficiency) is permitted.

11. There is a history of major diseases before the first dose

12. History of perforation of the gastrointestinal tract and/or fistula, history ofgastrointestinal obstruction (including incomplete intestinal obstruction requiringparenteral nutrition), extensive bowel resection (partial colectomy or extensivesmall bowel resection, complicated by chronic diarrhea) within 6 months before thefirst study drug administration.

13. Patients with >30 Gy of chest radiation therapy within 6 months prior to the firstdose, nonthoracic radiation therapy >30 Gy within 4 weeks prior to the first dose,and palliative radiation therapy of ≤30 Gy within 2 weeks prior to the first doseand failed to recover from the toxicity and/or complications of these interventionsto NCI CTCAE Grade ≤1 (except hair loss and fatigue). Palliative radiotherapy forsymptom control is permitted if it has been completed at least 2 weeks before thefirst dose, and no additional radiotherapy for the same lesion is planned.

14. Inactivated vaccines are allowed. Patients are excluded if they have received a livevaccine or live attenuated vaccine within 4 weeks prior to the first dose, or ifthey are scheduled to receive a live vaccine or live attenuated vaccine during thestudy period.

15. Severe infection within 4 weeks prior to the first dose, including but not limitedto comorbidities requiring hospitalization, sepsis, or severe pneumonia; activeinfection that has received systemic anti-infective therapy within 2 weeks prior tothe first dose (excluding antiviral therapy for hepatitis B or C)