A First-in-Human Study of YL217 in Patients With Advanced Solid Tumors

Open to people ages 18 years and up

• Informed of the study before the start of the study and voluntarily sign their name and date in the informed consent form (ICF)
• Able and willing to comply with protocol visits and procedures
• Aged ≥ 18 years
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
• Tumor types as below:

For Part 1 and Part 2: Pathologically confirmed diagnosis of an advanced solid tumor, including adenocarcinoma and neuroendocrine neoplasm in gastrointestinal (GI), esophagus, gastroesophageal junction, pancreas or ampulla, and other solid tumors.

For Part 3 (Histologically or cytologically confirmed diagnosis+ locally advanced unresectable or metastatic disease):CohortA（colorectal adenocarcinoma）: Have clear documentation of rat sarcoma (RAS), vrafmurine sarcoma viral oncogene homolog B (BRAF), and microsatellite instability/mismatch repair status. Participants must have received at least one line of prior cytotoxic chemotherapeutic regimen. CohortB（ Human Epidermal Growth Factor Receptor 2 （HER2）-negative gastric, esophageal or gastroesophageal junction adenocarcinoma）: Participants must have received at least one line of prior cytotoxic chemotherapeutic regimen. CohortC(pancreatic adenocarcinoma): Participants must have received at least one line of prior cytotoxic chemotherapeutic regimen. CohortD(other advanced solid tumors)

• Adequate organ and bone marrow function.
• Have at least 1 extracranial measurable tumor lesion.
• Adequate archival formalin-fixed paraffin embedded （FFPE） tissue from prior biopsy.

• Prior treatment with an agent targeting CDH17
• Prior discontinuation of a topoisomerase I inhibitor due to treatment-related toxicities.
• Have received a topoisomerase I inhibitor within 6 months before the first dose of study drug.
• Have received an ADC consisting of a topoisomerase I inhibitor.
• Concurrent enrollment in another clinical study, unless it is an observational clinical study.
• Inadequate washout period for prior anticancer treatment before the first dose of study drug
• Undergone major surgery within 4 weeks before the first dose of study drug or expect major surgery during the study.
• Received long term systemic steroids or other immunosuppressive therapy within 2 weeks before the first dose of study drug.
• Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study.
• Diagnosis or evidence of spinal cord compression or leptomeningeal carcinomatosis.
• Uncontrolled or clinically significant cardiovascular and cerebrovascular diseases.
• A history of non-infectious interstitial lung disease (ILD)/pneumonitis that requires steroids, current active ILD/pneumonitis.
• Have clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
• Uncontrolled third-space fluid that requires repeated drainage.
• Digestive system disease that may cause bleeding, perforation, jaundice, gastrointestinal obstruction.
• An active tuberculosis based on medical history.
• Known human immunodeficiency virus (HIV) infection.
• Active hepatitis C infection.