This is a phase I, two-part, multicenter, first-in-human study. The Part 1 study will assess the safety, tolerability, preliminary anti-tumor activities, PK profile, immunogenicity and biomarker of GenSci139 in participants with locally advanced or metastatic solid tumors, as well as identity MTD (if any) and RDE. The Part 2 study is to further evaluate the preliminary anti-tumor activities, safety, PK profile, immunogenicity and biomarker of GenSci139 at RDE dose levels with selected advanced cancers.

Inclusion Criteria:

• Has the ability to understand and the willingness to sign a written informed consent document (prior to the initiation dose of GenSci139 and any study procedures).
• Is willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures.
• Adult participants (≥18 years of age or acceptable age according to local regulations, whichever is older) at the time of voluntarily signing informed consent.
• Is able to provide tumor tissues. Fresh biopsy specimens or archival tumor tissue samples obtained after last treatment are strongly preferred, and if not available, providing other archival tumor tissue specimens or not may be enrolled after discussion with sponsor.
• Has at least one measurable lesion by RECIST v1.1.
• Has an eastern cancer collaboration group (ECOG) status of 0 or 1.
• Left ventricular ejection fraction (LVEF) ≥50%.
• Has a life expectancy of ≥ 3 months.
• Has adequate hematologic and organ function prior to initiation dose of GenSci139.
• Women of childbearing potential (WOCBP) must be willing to use adequate contraception while receiving GenSci139, and within 6 months after the last dose of GenSci139 and have a negative serum human chorionic gonadotropin (HCG) test.
• Nonsterile males must be willing to use adequate contraception for the duration of receiving GenSci139 and within 6 months after the last dose of GenSci139.
• Has histologically or cytologically confirmed locally advanced or metastatic UC, HNSCC, TNBC, NSCLC, BTC, ESCC, GC, CRC, OC, NPC, PDAC etc. and have progressed following standard therapy, or for whom, in the opinion of the investigator, no available and effective standard therapy exists.

Key Exclusion Criteria:

• Any active malignancy within 3 years before initiation dose of GenSci139 except for the cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, non-muscle invasive bladder cancer (NMIBC), carcinoma in situ of the cervix or breast).
• Has diagnosed as primary central nervous system (CNS) tumor.
• Has CNS metastases, unless asymptomatic, neurologically stable and not requiring steroids treatment for at least 4 weeks prior to initiation dose of GenSci139.
• Has a history of leptomeningeal disease or spinal cord compression.
• Has stroke or transient ischemic attack within 6 months prior to initiation dose of GenSci139.
• Active autoimmune diseases and inflammatory diseases.
• Has a history of (non-infectious) interstitial lung disease (ILD) / pneumonitis that required steroids, has current ILD / pneumonitis, or where suspected ILD / pneumonitis cannot be ruled out by imaging at screening.
• Unstable thrombotic events within 6 months prior to initiation dose of GenSci139.
• Has severe chronic or active infection
• Uncontrolled hypertension
• Has clinically significant cardiovascular disease
• Known severe hypersensitivity to GenSci139 and/or any of its excipients.
• Has a history of severe hypersensitivity reactions to other monoclonal antibodies
• With enough washout period to some therapies specified in protocol.
• Known HIV infection, active HBV or HCV infection.
• Has unresolved toxicities from previous anticancer therapy
• Had received HER2 or EGFR monoclonal antibodies, or using TOPO I inhibitor as payload, targeted to HER2 or EGFR ADC, and could not be intolerance of those treatment.
• Women who are pregnant or lactating or are planning to become pregnant.
• Uncontrollable pleural effusion, pericardial effusion, or abdominal and pelvic effusion requiring drainage and/or diuretics within 14 days prior to GenSci139 infusion.
• The other conditions of participation in this clinical trial were not considered appropriate by the investigators.