A Study of HBI-8000 (Tucidinostat) With Pembrolizumab in Non-Small Cell Lung Cancer

Exclusion Criteria

• •1. History of Grade ≥3 hypersensitivity reactions to monoclonal antibodies.
• •2. History of a cardiovascular illness including: QT interval corrected by heart rate using Fridericia's correction formula (QTcF) \>450 ms in male or \>470 ms in female, congenital long QT syndrome, congestive heart failure (New York Heart Association Grade III or IV) (Protocol Appendix 2); unstable angina or myocardial infarction within the previous 6 months; or symptomatic cardiac arrhythmia despite medical management.
• •3. Uncontrolled hypertension, systolic blood pressure (SBP) \>160 mmHg or diastolic blood pressure (DBP) \>100 mmHg.
• •4. Central nervous system metastasis or leptomeningeal disease except when treatment for brain metastasis is completed \>14 days prior to C1D1 and stable for ≥4 weeks on \<10 mg daily prednisone or equivalent.
• •5. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer disease or bowel resection that affects absorption of orally administered drugs.
• •6. Recurrent pleural effusion requiring repetitive palliative thoracentesis within 3 months prior to study entry, except for subjects with a pleurex port.
• •7. Active, known, or suspected autoimmune disease, or history of immune-mediated toxicity leading to treatment discontinuation, except for type I diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy.
• •8. Active pneumonitis, history of non-infectious pneumonitis that required treatment with steroids, or history of interstitial lung disease.
• •9. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
• •10. Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS).
• •11. Active hepatitis B (hepatitis B surface antigen \[HBVsAg\] positive), or hepatitis C (HCV antibody test or serum hepatitis C ribonucleic acid \[RNA\] positive).
• •12. Received approved live vaccines within 30 days of planned C1D1. Inactivated viral vaccines or vaccines based on subviral component are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are not allowed. COVID-19 vaccination should be administered \>7 days before C1D1.
• •13. Any condition requiring chronic systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications, or steroids use within 14 days of study drug administration. Inhaled or topical steroids are permitted.
• •14. Use of other investigational agent (drug not marketed for any indication) within 28 days or at least 5 half-lives (whichever is shorter) before study drug administration.
• •15. Pregnant or breast-feeding women.
• •16. Second malignancy unless in remission for 2 years; subjects with non-melanomatous skin cancer, carcinoma in situ of the cervix treated with curative intent, or curatively treated prostate cancer with prostate-specific antigen (PSA) \<2.0 ng/mL can be included.
• •17. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events.
• •18. Unwilling or unable to comply with procedures required in this protocol.