Phase I Open-Label Randomized Multicenter Study of XNW28012 Monotherapy in Metastatic Pancreatic Cancer

Inclusion criteria

• subjects with histologically or cytologically confirmed metastatic PDAC, whose disease has progressed after at least 1 prior systemic therapy.
• Age ≥ 18 years old at the time of consent.
• Subjects must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. ECOG status of 2 can be allowed if it is a result of disease progression and warrantsdiscussion with the medical monitor.
• Subjects must have adequate organ function within 7 days prior to the first study drug administration, as indicated by the following laboratory values;
• Life expectancy of at least 12 weeks.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose of study drug.
• Non-sterile subjects must be willing to use a highly effective contraception (e.g., IUD, pill, or condom) for the duration of the study and for 6 months after the last dose of study drug unless their partner is sterilized.
• Subjects are able to provide written informed consent, understand and are willing to comply with the requirements of the study.

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Exclusion criteria

• A history of severe infusion reactions to other monoclonal antibodies/antibody drug conjugates (ADCs), or allergic reactions to any components of XNW28012, or treatment with TF-directed therapy.
• Any anti-tumor therapy within 21 days prior to the first dose, including but not limited to: small molecules, immunotherapy, chemotherapy, monoclonal antibodies, or any other experimental drugs.
• Any active malignancy, with the exception of the specific types of cancersunder investigation in this study and any locally recurring cancer that has been treated curatively .
• Have received a live vaccine within 4 weeks prior to the first dose of study drug. Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed; however, intranasal influenza vaccines will not be allowed if they are attenuated live vaccines.
• Have received granulocyte colony stimulating factor (G-CSF) or granulocyte / macrophage colony stimulating factor support within 1 week before screening, or pegylated G-CSF within 2 weeks before screening.
• Subjects with toxicities (as a result of prior anti-cancer therapy) that have not improved to CTCAE grade ≤ 1 or stabilized, except those AEs not considered as a likely safety risk (e.g., alopecia).
• Any history of pneumonitis or interstitial lung disease (ILD).
• Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack) ≤ 3 months prior to screening is allowed if stable.
• Any hematological risk factors.
• Clinically significant cardiovascular/cerebrovascular conditions.
• Subjects have known active CNS metastases and/or carcinomatous meningitis.
• Active ocular surface disease at screening, or subjects with any prior episode of cicatricial conjunctivitis, or corneal nebula; subjects with glaucoma of CTCAE grade ≥ 2.
• Any history of Toxic Epidermal Necrolysis (TEN) or Steven Johnson Syndrome.
• Subjects who have undergone major surgery within 28 days prior to the first dose of study drug, except if the procedure is minimally invasive.
• Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is higher than 500 IU/mL or subjects with positive hepatitis C virus (HCV) RNA. Inactive hepatitis B surface antigen (HbsAg) carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL), and cured hepatitis C subjects may be enrolled.
• A known history of HIV infection or acquired immunodeficiency syndrome (AIDS).
• Subjects with severe chronic or active infections requiring antibacterial, antifungal or antiviral therapy.
• Known immunodeficiency or any condition that requires systemic treatment with either corticosteroids (≥ 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 7 days before the first dose of study drug.
• Subjects who have received (or plan to receive during the study treatment period) strong/moderate CYP3A4 inhibitors or inducers, or strong/moderate CYP2D6 inhibitors within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of study drug.
• Have an ongoing significant, uncontrolled medical condition.
• Subjects who are pregnant or breastfeeding or expecting to conceive within the projected duration of the study.
• Underlying medical conditions or alcohol, drug abuse or dependence that, in Investigator's opinion, will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or adverse events, or insufficient compliance during the study according to Investigator's judgment.