Rational EpigenetiC Immunotherapy for SEcond Line Therapy in Patients With NSCLC: PRECISE Trial

Inclusion Criteria

• Histologically or cytologically-proven NSCLC
• Subjects must have received 1 or more prior systemic therapies for this disease, should not have had prior treatment with immunotherapy; (including immune checkpoint inhibitor drugs, or immunotherapy vaccines); Patients with epidermal growth factor receptor (EGFR) or ALK alterations will need to have progressed on a TKI treatment
• Measurable disease per RECIST1.1
• Disease that can be accessed by a bronchoscopic, surgical or percutaneous biopsy
• Eligible for biopsy from safety perspective
• Agrees to percutaneous biopsy prior to study, may be eligible if archival tissue from a biopsy is after most recent therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥8.5g/dL or ≥5.6mmol/L
• Serum creatinine ≤1.5 times upper limit of normal
• Measured or calculated creatinine clearance ≥ 30mL/min for subject with creatinine levels > 1.5 times institutional upper level of normal (ULN)
• Serum total bilirubin ≤1.5 times upper limit of normal
• Direct bilirubin ≤ upper limit of normal for subjects with total bilirubin levels > 1.5 upper limit of normal
• AST (SGOT) ≤2.5 times upper limit of normal or ≤5 times upper limit of normal for subjects with liver metastases
• ALT (SGPT) ≤2.5 times upper limit of normal or ≤5 times upper limit of normal for subjects with liver metastases
• Albumin ≥ 2 mg/dL
• Patients with history of brain metastases can be eligible for study treatment at a minimum of 1 weeks following the completion of gamma knife or whole brain radiotherapy. (if patient underwent surgical resection of brain metastasis need to wait for 4 weeks before study treatment) Patients should ideally be off steroids at the start of study treatment, however patients on steroid taper and dose of no more than 2mg/day of Decadron at the time of study treatment are allowed; and steroids should be tapered off as quickly as clinically feasible.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically unstable bleeding or pulmonary embolism leading to hemodynamic compromise are not allowed
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness (HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with oral THU-Dec. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated.
• Pregnancy or breastfeeding (pregnant or breastfeeding women are excluded from this study because oral THU-Dec has the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with oral THU-Dec, breastfeeding should be discontinued if the mother is treated with oral THU-Dec.
• Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due