Double-blind Study to Evaluate the PK, Efficacy, Safety and Immunogenicity of MB12 Versus Keytruda® in Stage IV NSCLC

Inclusion Criteria:

Individuals must meet all of the following criteria to be included in the study:

1. Willing and able to provide written informed consent for the study before theinitiation of any study-specific procedures.

2. Greater than or equal to 18 years of age at the time of signing the ICF.

3. Body weight ≥50 kg at Screening.

4. Having newly diagnosed stage IV (defined by the eighth edition of the TNMclassification) non-squamous NSCLC, without prior systemic treatment for thedisease. For those subjects in whom the pleural or pericardial effusion is the onlylocation of metastatic disease, confirmation of its malignant etiology is required.

5. At least 1 radiographically measurable lesion per RECIST version 1.1, locallyassessed.

6. Programmed death-ligand 1 (PD-L1) expression ≥50%, locally determined byimmunohistochemistry, as determined by a Food and Drug Administration (FDA)validated method.

7. Life expectancy of at least 3 months.

8. ECOG performance status of 0 to 1.

9. Adequate hepatic, renal, hematologic, endocrine, and coagulation function, definedas:

10. Liver function: bilirubin level ≤1.5 × the upper limit of normal (ULN) (≤3 ×ULN for subjects with Gilbert's syndrome), albumin level ≥ lower limit ofnormal (LLN), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 × ULN in subjects without liver metastases or ≤5 × ULN in subjects withliver metastases.

≤1.5 × ULN, calculated creatinineclearance ≥50 mL/min (Cockcroft-Gault formula).

3. Hematologic function: absolute neutrophil count ≥1.5 × 109/L; platelet count ≥100 × 109/L, hemoglobin ≥9 g/dL.

4. Endocrine function: thyroid stimulating hormone (TSH) within normal limits. IfTSH is not within normal limits, the subject may still be eligible if T3 andfree T4 are within normal limits.

5. Coagulation: international normalized ratio (INR) and activated partialthromboplastin time (aPTT) ≤ 1.5 × ULN unless subject is receivinganticoagulant therapy. Subjects on anticoagulant therapy must be on a stableanticoagulation regimen and have an INR not above the target therapeutic rangefor the 14 days before the first dose of the study drug.

6. Subjects with a negative COVID-19 test (done at the discretion of investigator orper local regulation) within previous 24 hours before randomization. In case ofconfirmed COVID-19 infection before Screening, documentation of resolution ofinfection by appropriate laboratory test is required.

7. No history of prior malignancy, except for basal cell carcinoma of the skin,superficial bladder cancer, squamous cell carcinoma of the skin, or cervical cancerin situ, or has undergone potentially curative therapy without evidence of diseaserecurrence for 3 years from the start of that therapy.

8. Women of childbearing potential (WOCBP) must either abstain from sexual intercourseor employ highly effective contraception measures during the study and for at least 6 months after the last dose of the study drug. Highly effective measures include 2forms of contraception. Postmenopausal or surgically sterile women (ie,hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) are eligible.Postmenopausal status is defined as either: amenorrheic for ≥12 months followingcessation of exogenous hormonal treatments and without an alternative medical cause;luteinizing hormone and follicle stimulating hormone levels in the postmenopausalrange for women under 50 years of age; radiation-induced ovarian ablation with lastmenses ≥1 year ago; or chemotherapy-induced menopause with a ≥1-year interval sincelast menses. Female subjects must refrain from donating or banking eggs (ova,oocytes) and retrieving eggs for use during study treatment and for 6 months afterthe last dose of the study drug.

9. Male subjects, if not surgically sterile, must either abstain from sexualintercourse or employ highly effective contraception (condoms or other barrier formsof contraception) during the study and for at least 6 months after the last dose ofthe study drug. Male subjects should also avoid semen donation or providing semenfor in-vitro fertilization during the above mentioned duration.

Exclusion Criteria:

1. Unwilling or unable to comply with scheduled visits, drug administration plan,laboratory tests, or other study procedures and study restrictions.

2. Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by thepredominant cell type; if small cell elements are present, the subject isineligible.

3. Participation in another clinical trial or treatment with another investigationalagent within 4 weeks or 5 half-lives before randomization, whichever is longer.

4. Known actionable mutations for which there is an approved and available therapy.

5. Known central nervous system metastases and/or carcinomatous meningitis.

6. Previous systemic steroid therapy (prednisone at a dose of 10 mg or equivalent)within 3 days before the first dose of the study drug or receiving any other form ofimmunosuppressive medication. Subjects receiving daily steroid replacement therapy (daily prednisone at a dose of 5 to 7.5 mg or equivalent) could be included in thestudy.

7. Subject who requires any other form of localized or systemic antineoplastic therapyduring the study.

8. Prior anti-programmed cell death-1 (anti-PD-1), anti-PD-L1, anti programmeddeath-ligand 2 (anti-PD-L2), anti-CD137, or anti cytotoxic T lymphocyte antigen (CTLA)-4 therapy (including ipilimumab or any other antibody or drug thatspecifically targets co stimulation of T cells or immune checkpoints).

9. Prior systemic cytotoxic chemotherapy, biological therapy, or major surgery within 3weeks before the first dose of the study drug; have received thoracic radiationtherapy of >30 gray (Gy) within 6 months before the first dose of the study drug.Palliative radiotherapy is allowed if completed >14 days before the first dose ofthe study drug.

10. Known history of severe hypersensitivity to another monoclonal antibody.

11. Active autoimmune disease which has required systemic treatment in the last 2 yearsbefore the first dose of the study drug (eg, disease modifying agents,corticosteroids, or immunosuppressive treatment). Replacement therapy (eg,thyroxine, insulin, or physiological corticosteroid replacement therapy forpituitary or adrenal insufficiency) is not considered a form of systemic treatment.

12. Interstitial lung disease or pneumonitis requiring oral or intravenous steroids.

13. Active infection or a previous infection requiring intravenous systemic treatmentwithin 30 days before the first dose of the study drug.

14. Subject who has received or is about to receive a live virus vaccination within 30days before the first dose of the study drug. Seasonal flu and COVID-19 vaccinesthat do not contain live virus are permitted.

15. Known history of human immunodeficiency virus (HIV)-1 or HIV-2.

16. Known active tuberculosis or hepatitis B (hepatitis B surface antigen [HBsAg]positive) or hepatitis C (hepatitis C antibody positive and hepatitis C virus [HCV]RNA positive).

17. Subject who has received a solid organ/tissue allogeneic transplant.

18. Known psychiatric disorders that could interfere with cooperation with studyrequirements.

19. At the time of signing the ICF, the subject is a regular user (including "recreational use") of any illicit drug or has a recent history (within the pastyear) of substance abuse (including alcohol).

20. Subject is pregnant or lactating or expecting to conceive during the study or up to 120 days after the last dose of the study drug.

21. Immediate family member who is at the research site or sponsoring staff who isdirectly involved in this study