A Study of ES102 (OX40 Agonist) in Combination With JS001 in Patients With Advanced Solid Tumors

Inclusion Criteria:

• 1.Males or females aged ≥18 years.

• 2.Ability to understand and the willingness to sign a written informed consent form.

• 3.Subjects with pathological or cytological diagnosed advanced solid tumor, whosedisease has progressed despite standard therapies, or for whom no further standardtherapy exists, or who is unsuitable for available standard therapies and at leasthas progressed after receiving first line therapy.

• 4.PD-L1 by IHC: Parts 1 and Part 2 D2-D3: IHC result mandatory but any scoreallowed. Part 2 D1: Tumor Proportion Score (TPS) ≥ 1%.

• 5.At least one measurable lesion is required (RECIST v1.1)

• 6.Adequate hematologic, coagulation, hepatic and renal function as defined perprotocol.

• 7.Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.

• 8.Estimated life expectancy, in the judgment of the investigator, of at least 12weeks.

• 9.Male and female subjects of childbearing potential and their spouses must bewilling to use feasible contraceptive methods considered effective by theinvestigator, from the time of signing informed consent and for the duration ofstudy participation through 3 months, following the last dose of study drug.Postmenopausal women are considered to have no fertility potential only ifmenostasis lasts for at least 12 months.

Exclusion Criteria:

• 1.Prior exposure to OX40 agonists.

• 2.Receipt of any anticancer investigational product or any approved anticancerdrug(s) or biological product(s) within 4 weeks prior to the first dose of studydrug with certain exceptions.

• 3.Receipt of non-CNS adjuvant radiation therapy within 1 week prior to the firstdose, receipt of radiation therapy within 2 weeks or with radiation pneumonia, havenot recovered from radiation-related toxicity or still require hormonal treatmentfor radiation-related toxicity.

• 4.Known allergies to CHO-produced antibodies, which in the opinion of theInvestigator suggests an increased potential for an adverse hypersensitivity toES102.

• 5.Subjects with allergic reactions to the active ingredients of JS001 or any of theexcipients.

• 6.Treatment with systemic immunosuppressive medications within 4 weeks prior to thefirst dose of study drug. Certain exceptions as defined in protocol apply.

• 7.Receipt of live viral vaccine treatment within 4 weeks prior to the first dose ofthe study drug.

• 8.Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.

• 9.Subjects with primary or metastatic brain or meningeal tumors.

• 10.Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead todiscontinuation of prior immunotherapy. Some exceptions as defined per protocolapply.

• 11.Subject has not recovered from all AEs of previous anticancer therapies tobaseline or ≤ Grade 1 per CTCAE v5.0 before the first dose of study drug. Certainexceptions as defined in protocol apply.

• 12.Hematologic malignancies.

• 13.Receipt of treatment with G-CSF, GM-CSF, Thrombopoietic drugs or EPO within 14days prior to the first dose of the study drug.

• 14.Patients with other malignancies within 2 years before screening shall beexcluded in Part B. Some exceptions as defined per protocol apply.

• 15.Active autoimmune disease or documented history of autoimmune disease thatrequired systemic steroids or other immunosuppressive medications. Certainexceptions as defined in protocol apply.

• 16.Active interstitial lung disease (ILD) or pneumonitis or a history of ILD orpneumonitis requiring treatment with steroids or other immunosuppressivemedications.

• 17.Clinically significant cardiac condition, including myocardial infarction,uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heartdisease < 6 months; left ventricular ejection fraction (LVEF) < 50%; New York HeartAssociation (NYHA) Class III or IV congestive heart failure; or uncontrolledhypertension.

• 18.History of pulmonary embolism within 12 weeks prior to the first dose of studydrug administration.

• 19.Major surgery within 4 weeks prior to enrollment on this trial.

• 20.History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)infection for Part 1. Exceptions as defined in protocol for Part 2 will apply.

• 21.Receiving the systemic anti-infectious drug treatments within 4 weeks prior tothe first dose of study drug.

• 22.Pregnant or nursing females.

• 23.Any known, documented, or suspected history of substance abuse that wouldpreclude subject from participation, certain exceptions as defined in protocolapply.

• 24.The subject is inappropriate to participate in this study for other reasons inthe judgment of the Investigator.