A Study of ES102 in Combination With Toripalimab in Subjects With Advanced Non-small Cell Lung Cancer

Inclusion Criteria: * Having sufficient understanding of this study and being willing to sign the informed consent form (ICF). * Males or females, age 18-75 years at the time of signing the informed consent form. * Histologically or cytologically confirmed, unresectable locally advanced and metastatic non-small cell lung cancer not suitable for radical concurrent chemoradiotherapy. * Without known EGFR mutation/ALK fusion/ROS1 fusion gene. * Previous failed concurrent or sequential treatment with systemic platinum-containing chemotherapy and PD-1/PD-L1 inhibitor therapy for NSCLC that cannot be radically resected or not suitable for radical concurrent radio chemotherapy. * Five consecutive unstained slides from formalin-fixed paraffin-embedded (FFPE) tumor tissue (archived tumor tissue up to 5 years or freshly biopsied tumor tissue) sources are available for PD-L1 testing in the central laboratory. * PD-L1 TPS ≥50% by 22C3 antibody IHC assay in the central laboratory. * At least one measurable lesion (in accordance with RECIST v1.1). * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. * Estimated life expectancy of at least 3 months. * Adequate hematologic, hepatic, renal and coagulation function as defined per protocol. * Male and female subjects of childbearing potential must be willing to be completely abstinent or to use a highly effective method of contraception (i.e., a failure rate of less than 1%) from the time of signing the informed consent form until 3 months after the last dose of study drug. Exclusion Criteria: * Any prior therapy targeting OX40. * Receipt of any other investigational drug or device intervention within 28 days prior to the first dose of the study drug. * Receipt of anticancer Chinese herbal therapy within 14 days prior to the first dose of the study drug. * Receipt of radiotherapy within 14 days prior to the first dose of the study drug. * Receipt of any other anti-cancer drug(s) including chemotherapy, targeted therapy, immunotherapy, biotherapy, etc., within 28 days or 5 half-lives prior to the first dose of the study drug. * Prior allogeneic or autologous bone marrow transplant or solid organ transplant. * The toxicity from prior anti-cancer therapies has not resolved to ≤ Grade 1 per NCI-CTCAE v5.0. Certain exceptions as defined in protocol apply. * Systemic glucocorticoids (e.g., \>10 mg/day of prednisone or equivalent doses of similar drugs) or other immunosuppressive agents were required for systemic treatment within 14 days prior to the first dose of the study drug or during the study period. * Major surgery within 28 days prior to the first dose of the study drug. * Receipt of live viral vaccine treatment within 28 days prior to the first dose of the study drug. * Known allergy to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for hypersensitivity to ES102. * Subjects with an allergic reaction to the active ingredients ofToripalimab or any of the excipients. * Known allergy to the pre-medication prescribed in the protocol and unable to receive pre-medication. * History of invasive malignant tumors other than the study disease within the past two years. Some exceptions as defined per protocol apply. * History of immune-related adverse events (irAEs) of Grade ≥3 or those that led to discontinuation of treatment. Some exceptions as defined per protocol apply. * Active autoimmune disease or a known history of autoimmune disease requiring systemic corticosteroid or immunosuppressive treatment. * Active interstitial lung disease (ILD) or pneumonia; or a history of ILD or (non-infectious) pneumonia requiring corticosteroid or other immunosuppressive treatment. * Central Nervous System (CNS) metastases. * Active infection requiring systemic treatment; Human Immunodeficiency Virus (HIV) infection (HIV antibody positive); Hepatitis B Virus (HBV) infection (HBsAg positive) or Hepatitis C Virus (HCV) infection (HCV antibody positive). Some exceptions as defined per protocol apply. * Cirrhosis, alcoholic hepatitis, drug-induced hepatitis, non-alcoholic steatohepatitis, and hereditary liver diseases. * History or evidence of cardiovascular abnormalities. * Pregnant or breastfeeding women. * Any known, documented, or suspected history of substance abuse that would preclude subject from participation, certain exceptions as defined in protocol apply. * Any other disease or clinically significant abnormal laboratory parameters that investigator considers may compromise subject safety or study integrity, interfere with subject participation in the trial, or affect the study objectives, including serious medical or psychiatric illness/condition. * Personnel involved in the design and/or implementation of the study (applicable to sponsor/CRO personnel and site personnel). * Subjects are unable to comply with the study procedures, restrictions and requirements, in the opinion of Investigator.