This is an open-label, dose-escalation study of the study drug YH002. The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of YH002 in patients with advanced solid Malignancies

This is a single arm clinical trial in subjects with advanced solid tumor receiving multiple doses of YH002 intravenously (IV). YH002 will be administered (IV) in 6-48 patients with advanced solid tumors. An accelerated titration method followed by a traditional 3+3 dose escalation algorithm will be utilized to determine MTD/MAD. Patients will be dosed at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F, Dose G, and Dose H every 3 weeks (Q3W).

Inclusion Criteria:

• Male or female, aged ≥ 18 years
• Confirmed as histologically or cytologically, locally advanced or metastatic non-resectable solid tumors, must have received and progressed on, or been ineligible for, or intolerant of available standard therapies known to confer clinical benefit or for whom no standard therapy exits
• Subjects enrolled in Dose D, Dose E, Dose F, Dose G, and Dose H cohorts must have at least one measurable lesion per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 and life expectancy no less than 3 months
• Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy

Exclusion Criteria:

• Symptomatic central nervous system (CNS) metastases. Subjects with asymptomatic CNS metastases who are radiologically and neurologically stable ≥ 4 weeks following CNS- directed therapy, and do not require corticosteroids or anticonvulsants are eligible for study entry
• Received anticancer therapy or radiation therapy within 5 half-lives or 4 weeks prior to study entry, whichever is shorter
• Received palliative radiotherapy to a single area of metastasis within 2 weeks prior to study entry
• Received agonist antibodies to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies prior to the study entry
• Allergy or sensitivity to YH002, or known allergies to antibodies produced from Chinese hamster ovary cells which assessed to increase the potential for an adverse hypersensitivity to YH002 by Investigator
• History of a Grade 3-4 allergic reaction to treatment with another monoclonal antibody
• Grade ≥3 irAEs or irAEs that lead to discontinuation of prior immunotherapy. Hypothyroidism, Type 1 DM, and dermatologic irAEs (except previous Steven Johnson Syndrome, toxic epidermal necrolysis, or other severe forms of dermatitis). Type 1 DM should be controlled with reduction of toxicity to Grade 1 or less
• Concomitant active autoimmune disease or history of autoimmune disease requiring systemic treatment or history of autoimmune disease within 2 years prior to study entry (except vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by replacement therapy)
• Received steroids or other immunosuppressive systemic therapy within 4 weeks prior to the first dose of the study drug, or has need to be treated during the study (except using on low systemic absorption location prevent or treat non- autoimmune condition)
• Active hepatitis B or C. Hepatitis B carriers without active disease or cured Hepatitis C may be enrolled
• Severe cardiovascular disease within 6 months of study entry