A Study to Compare the Efficacy and Safety of YL201 With Standard Chemotherapy in Patients With Metastatic Pancreatic Cancer After Failure of Gemcitabine-Based Systemic Chemotherapy

A Randomized, Controlled, Multicenter Phase III Study to Evaluate the Efficacy and Safety of YL201 Versus Liposomal Irinotecan in Combination With 5-Fluorouracil/Leucovorin in Participants With Metastatic Pancreatic Ductal Adenocarcinoma Who Have Failed Prior Gemcitabine-based Systemic Therapy

The purpose of this study is to evaluate the safety and efficacy of an investigational B7-H3 antibody drug-conjugate administered as monotherapy, compared with standard of care (SOC) chemotherapy in metastatic pancreatic cancer patients who have failed prior Gemcitabine-based systemic therapy.

Inclusion Criteria:

1. Participants must voluntarily sign a written informed consent form (ICF) and be willing and able to comply with protocol requirements.
2. Participants must be ≥18 and ≤75 years of age.
3. Participants must have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
4. Participants must have a life expectancy of at least 3 months.
5. Participants must have histologically or cytologically confirmed incurable metastatic pancreatic ductal adenocarcinoma (PDAC).
6. Participants must have received and failed only one prior line of gemcitabine-based systemic therapy.
7. Participants must have at least one measurable lesion according to RECIST v1.1.
8. Participants must have adequate organ function as defined in the protocol.
9. Participants must agree to follow the contraception requirements specified in the protocol.

Exclusion Criteria:

1. Participants with another malignancy within 5 years before randomization.
2. Participants with pathologically confirmed pancreatic cancer other than PDAC.
3. Participants who have previously received B7-H3-targeted therapy.
4. Participants who have previously received topoisomerase I inhibitor or antibody-drug conjugate containing topoisomerase I inhibitor.
5. Participants who are concurrently enrolled in another clinical study, unless it is an observational, non-interventional study or the participant is in the follow-up period of an interventional study.
6. Participants who have not met the protocol-specified washout requirements for prior systemic therapy, relevant concomitant medications, radiotherapy, or surgery before randomization, or who have not adequately recovered from prior surgery or are planning to undergo major surgery during the study.
7. Participants with protocol-specified exclusionary conditions related to central nervous system (CNS) metastases, history of transplantation, immunosuppressive therapy, live vaccine administration, or autoimmune or inflammatory diseases.
8. Participants with uncontrolled or clinically significant concomitant diseases, including serious gastrointestinal, cardiovascular or cerebrovascular, pulmonary, thromboembolic, bleeding-related, effusion-related, or ascites-related safety risks.
9. Participants with recent serious infection, active infection, active tuberculosis or syphilis, HIV positivity or immunodeficiency, or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
10. Participants with unresolved toxicity from prior anticancer therapy that has not recovered to the level specified in the protocol.
11. Participants with known hypersensitivity to any component of the study treatment, or a history of severe hypersensitivity reactions or severe infusion-related reactions.
12. Participants who are pregnant or breastfeeding, planning to become pregnant or breastfeed, or who have any other medical, psychiatric, social, or compliance-related factors that, in the investigator's opinion, would make them unsuitable for participation in the study.