A Phase II Clinical Study to Evaluate HLX43 in Subjects With Advanced Pancreatic Cancer

Prior treatment

• Prior treatment with an antibody-drug conjugate (ADC) of topoisomerase I;
• Received radical radiotherapy within 3 months prior to the first dose;
• History of an adverse event that led to permanent discontinuation of prior immunotherapy, or a history of ≥ Grade 2 immune-mediated pneumonitis or immune-mediated myocarditis;
• History or presence of clinically significant pulmonary impairment due to concurrent lung disease, Subjects with a history of radiation pneumonitis within the past 6 months are also excluded;
• Use of strong CYP2D6/CYP3A inhibitors/inducers within 2 weeks pre-randomization;
• Systemic corticosteroid use (\>10mg prednisone/day equivalent) or immunosuppressants within 2 weeks pre-randomization. Exceptions: Topical/ocular/intra-articular/nasal/inhaled steroids; short-term prophylactic use for contrast agents;
• Live/attenuated vaccines within 4 weeks pre-randomization;
• Undergone biliary stent placement within 7 days prior to randomization, or has unrelieved biliary or duodenal obstruction despite active treatment;

Other illness

• Histologically or cytologically confirmed as other pathological types of pancreatic cancer or containing components of other pathological differentiation;
• History of other malignancies within 2 years prior to randomization (except radically treated early-stage malignancies);
• Presence of spinal cord compression or clinically active central nervous system metastases (defined as untreated or symptomatic metastases, or those requiring corticosteroids or anticonvulsants), carcinomatous meningitis, or leptomeningeal disease;
• Poorly controlled cardiovascular/cerebrovascular conditions;
• Active systemic infections requiring IV antibiotics within 2 weeks pre-randomization;
• Active/suspected autoimmune diseases. Exceptions: Hypothyroid patients on thyroid replacement; controlled type 1 diabetes with insulin;
• History of severe hypersensitivity to biologics/monoclonal antibodies or trial drug components;
• Active tuberculosis;
• Immunodeficiency disorders (HIV-positive or congenital/acquired immune deficiencies);
• Active HBV/HCV infection or co-infection;
• Suspected acute pancreatitis or a history of pancreatitis requiring clinical intervention recently;

Other

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Pregnant/lactating women;
• Investigators' judgment of clinical/lab abnormalities or other factors making participation inappropriate.

• Fully understand the study content, procedures, and potential adverse reactions before the trial, sign the informed consent form (ICF), voluntarily participate in the trial, and be able to complete the study per the protocol requirements;
• Age ≥ 18 years, ≤75 years, at the time of signing the ICF, regardless of gender;
• Histologically or cytologically confirmed, unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC),who has failed at least one prior line of standard systemic therapy. The prior therapy must have included a fluoropyrimidine-based or gemcitabine-based regimen;
• At least one measurable lesion per RECIST v1.1 within 4 weeks before randomization;
• Willing to provide archived (preferably within 2 years) or fresh tumor tissue specimens for the detection of PD-L1 expression.
• At least 3 weeks (or 5 half-lives, whichever is shorter) since last major surgery, medical device treatment, radiotherapy (except palliative bone radiotherapy), cytotoxic chemotherapy, immunotherapy, or biological therapy; ≥2 weeks since last hormonal therapy or small molecule targeted therapy; ≥1 week since last traditional Chinese medicine treatment with anti-tumor indications or minor surgery; with treatment-related adverse events recovered to CTCAE v5.0 ≤ grade 1 (except grade 2 peripheral neuropathy and alopecia);
• ECOG performance status 0-2 within 1 week before randomization;
• Expected survival ≥ 3 months；
• Adequate organ function within 1 week before randomization (no blood transfusion or colony-stimulating factors within 14 days prior to first dose)
• Fertile participants must use ≥1 highly effective contraceptive method during the trial and for ≥6 months after last dose; females of childbearing potential must have negative pregnancy test within 7 days before enrollment.