A Trial of YL-13027 in Combination With Gemcitabine and Nab-paclitaxel in Patients With Refractory Metastatic Pancreatic Cancer

Exclusion Criteria

• •1. Prior therapy with a TGF-β pathway-targeted agent.
• •2. Prior treatment with gemcitabine, nab-paclitaxel, or the combination of gemcitabine and nab-paclitaxel.
• •3. Unresolved toxicities from prior therapy (defined as having not resolved to NCI CTCAE v.5.0 Grade ≤1 or baseline) or any other toxicity that is deemed irreversible by the investigator. Exceptions include endocrinopathies from prior therapy or disease and successfully treated (such as hypothyroidism, diabetes mellitus), alopecia, vitiligo, and Grade ≤2 peripheral neuropathy.
• •4. Known symptomatic brain metastases or primary CNS malignancy. Participants who have stable symptoms and are requiring steroids of 4 mg/day dexamethasone equivalent or less for 2 weeks prior to enrollment are permitted.
• •5. Live vaccines within 30 days prior to study treatment initiation.
• •6. Human immunodeficiency virus (HIV) infection with a current history of acquired immunodeficiency syndrome-defining illness or HIV infection with CD4+ T cell count \<350 cells/µL and HIV viral load more than 400 copies/µL.
• •7. Participants with active viral (any etiology) hepatitis are excluded. However, participants with serologic evidence of chronic hepatitis B virus (HBV) infection (positive hepatitis B surface antigen test and a positive hepatitis B core antibody test) who have a viral load below the limit quantification (HBV DNA titer \<1000 cps/mL or 200 IU/mL) and are not currently on viral suppressive therapy may be eligible and should be discussed with the principal investigators (PIs) and IND Sponsor. The addition of HBV suppressive medication (i.e., entecavir) should be considered during the period of study treatment. Participants with a history of hepatitis C virus infection who have completed curative antiviral treatment and have a viral load below the limit of quantitation may be eligible and should be discussed with the PIs and Investigational New Drug (IND) Sponsor.
• •8. Any of the following cardiac criteria experienced currently or within 6 months prior to enrollment: a. Congestive heart failure (New York Heart Association Functional Classification of ≥ Class 2) b. Acute coronary syndrome c. Clinically significant cardiac arrhythmia
• •9. Mean QTcF \>470 ms at screening.
• •10. Left ventricular ejection fraction \<50% or the lower limit of normal (per institutional standard) at screening.
• •11. Use of strong CYP3A inhibitors or inducers are prohibited within 14 days or 5 halflives, whichever is longer, prior to study treatment initiation and during the study treatment. For a comprehensive list of CYP3A inhibitors/inducers, refer to: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-anddrug-interactions-table-substrates-inhibitors-and-inducers.
• •12. Evidence of severe or uncontrolled systemic comorbidities (e.g., active bleeding diatheses or active infection), as determined by the investigator.
• •13. Participants who are pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 3 months after the last dose of study treatment.
• •14. Any condition that impairs a participant's ability to swallow whole pills or presence of active GI disease or other condition that will significantly interfere with the absorption, distribution, metabolism, or excretion of YL-13027, as determined by the investigator.
• •15. Any known psychiatric, substance abuse, or other disorder that would interfere with cooperation with the requirements of the study, in the opinion of the investigator.
• •16. Participants who are receiving any other investigational agents.
• •17. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.