HX008 Plus Chemotherapy VS Pembrolizumab Plus Chemotherapy As the First-line Treatment in Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer

Inclusion Criteria:

• Understood and signed an informed consent form.
• Age ≥ 18 years old, male or female.
• Have a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-AJCC 7th edition) nonsquamous NSCLC.
• Have not received prior systemic treatment for their advanced/metastatic NSCLC.Subjects who received adjuvant or neoadjuvant therapy are eligible if theadjuvant/neoadjuvant therapy was completed at least 12 months prior to the developmentof metastatic disease.
• Have confirmation that EGFR or ALK-directed therapy is not indicated.
• Have at least one measurable lesion according to RECIST1.1. Lesions situated inpreviously irradiated areas could be considered as target lesions if progression hasbeen demonstrated in such lesions. If measurable lesions exist in other areas, lesionsin previous irradiated areas should be considered as non-target lesions.
• Have provided tumor tissue from locations not radiated prior to biopsy fordetermination of PD-L1 status prior to randomization. Formalin fixed specimens thesubject has been diagnosed with metastatic disease will be preferred. Biopsiesobtained prior to receipt of adjuvant/neoadjuvant chemotherapy will be permitted ifrecent biopsy is not feasible.
• Life expectancy ≥ 3 months.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)Performance Score.
• Have adequate organ function as indicated by the following laboratory values:

1. Blood routine: serum albumin ≥2.5g/dL; absolute neutrophil count (ANC) ≥1.5×10^9/L; while blood cell count (WBC) ≥3×10^9/L; platelet count (PLT) ≥100×10^9/L; hemoglobin (HGB) ≥90 g/L (without blood transfusion within 4 weeksprior to enrollment);
2. Renal function: creatinine clearance (CrCl) ≥50 mL/min;
3. Liver function: Patients without liver metastases require alanineaminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. Patientswith liver metastases require: ALT and AST≤5×ULN. Serum total bilirubin ≤1.5xULNor direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN;
4. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unlessthe subject is receiving anticoagulant therapy; OR activated PartialThromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤1.5 X ULN unlessthe subject is receiving anticoagulant therapy.

• If female of childbearing potential, have a negative urine or serum pregnancy testwithin 72 hours prior to receiving the first dose of study medication. If the urinetest is positive or cannot be confirmed as negative, a serum pregnancy test will berequired.
• If female of childbearing potential, be willing to use an adequate method ofcontraception as outlined in Section 4.3-Contraception, for the course of the studythrough 120 days after the last dose of study medication or through 180 days afterlast dose of chemotherapeutic agents as specified in the protocol. If male subjectwith a female partner(s) of child-bearing potential, must agree to use an adequatemethod of contraception as outlined in Section 4.3-Contraception, starting with thefirst dose of study therapy through 120 days after the last dose of study therapy orthrough 180 days after last dose of chemotherapeutic agents as specified in theprotocol. Males with pregnant partners must agree to use a condom; no additionalmethod of contraception is required for the pregnant partner. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraceptionfor the subject.

Exclusion Criteria: The subject must be excluded from participating in the trial if the subject:

• Has predominantly squamous cell histology NSCLC. Mixed tumors will be categorized bythe predominant cell type; if small cell elements are present, the subject isineligible.
• Before the first dose of trial treatment:

1. Has received prior systemic cytotoxic chemotherapy or other antineoplastictherapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease
2. Had major surgery within 3 weeks prior to the first dose of trial treatment
3. Has participated in other clinical trial within 4 weeks prior to the first dose
4. Received radiation therapy to the lung that is > 30 Gy within 6 months prior tothe first dose
5. Completed palliative radiotherapy within 7 days prior to the first dose
6. Has received a live-virus vaccination within 30 days prior to the first dose.Seasonal flu vaccines that do not contain live virus are permitted.

• Has clinically active diverticulitis, intra-abdominal abscess, GI obstruction,peritoneal carcinomatosis.
• Suffered from other malignant tumors in the past 5 years, except those with low riskof metastasis and death (5-year survival rate > 90%), for instance, skin basal cellcarcinoma, squamous cell carcinoma, and carcinoma in situ from cervix or other regionsthat have been adequately treated.
• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Subjects with previously treated brain metastases may participate providedthey are clinically stable for at least 2 weeks and, have no evidence of new orenlarging brain metastases and also are off steroids 3 days prior to dosing with studymedication. Stable brain metastases by this definition should be established prior tothe first dose of study medication. Subjects with known untreated, asymptomatic brainmetastases (ie, no neurological symptoms, no requirements for corticosteroids, no orminimal surrounding edema, and no lesion >1.5 cm) may participate but will requireregular imaging of the brain as a site of disease.
• Has a known sensitivity to macromolecular agents or any component of cisplatin,carboplatin or pemetrexed.
• Has a history of organ or stem-cell transplantation.
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressivedrugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency, etc.) is not considered aform of systemic treatment.
• Has received systemic corticosteroids (a calculated dose >10mg prednisone per day ) orother immunosuppressive drugs within 14 days before the first administration of thestudy drug, excluding:

1. Nasal spray, inhalation or other local glucocorticoids.
2. Short-term (≤ 7 days) use of glucocorticoids as a preventive medication forallergic reactions or as a therapeutic medication for non-autoimmune diseases.

• Is on chronic systemic steroids. Subjects with asthma that require intermittent use ofbronchodilators, inhaled steroids, or local steroid injections would not be excludedfrom the study.
• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs),other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period forlong-acting agents, such as piroxicam).
• Is unable or unwilling to take folic acid or vitamin B12 supplementation.
• Had prior treatment with any anti-PD-1, or PD-L1 or PD-L2 agent or an antibodytargeting other immuno-regulatory receptors or mechanisms. Examples of such antibodiesinclude (but are not limited to) antibodies against IDO, PD-L1, IL-2R, GITR.
• Has a severe active infection prior to the first administration of the study drug andmight not in the best interest of the subject to participate, in the opinion of theInvestigator.
• Has known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodiespositive).
• Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positiveHBsAg result. Active Hepatitis C is defined by a known positive Hep C Ab result andknown quantitative HCV RNA results greater than the lower limits of detection of theassay. Those with HBV DNA viral load or copy number lower than the lower limits ofdetection of the assay or HCV RNA negative after adequate treatment is eligible.
• Has known psychiatric or mental disorders, such as epilepsy, dementia, or a knownregular user of any illicit drugs, or had a recent history (within the last year) ofsubstance abuse (including alcohol) that would interfere with cooperation with therequirements of the trial.
• Has symptomatic ascites or pleural effusion. A subject who is clinically stablefollowing treatment for these conditions (including therapeutic paracentesis) iseligible.
• Has a history of non-infectious pneumonitis that required steroids or activeinterstitial pneumonia. Other moderate and severe lung diseases that may interferewith the detection or treatment of study drug-related pulmonary toxicity or seriouslyaffect respiratory function, such as idiopathic pulmonary fibrosis, organic pneumonia / bronchiolitis obliterans, etc (except for local pneumonia induced by radiotherapy).
• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the study.
• Has active tuberculosis.
• Has uncontrolled systemic diseases, for instance, cardiovascular and cerebrovasculardisease, diabetes, hypertension, etc.
• Has a history or current evidence of any condition, or laboratory abnormality thatmight not in the best interest of the subject to participate, in the opinion of theInvestigator.