Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer

Inclusion Criteria:

• Male or female subjects, age ≥ 18 years.
• Histological or cytological diagnosis of small cell lung cancer. Subjects must have extensive-stage disease is defined as disease beyond the ipsilateral hemithorax, mediastinum and ipsilateral supraclavicular area and including malignant pleural or pericardial effusion or hematogenous metastases.
• Patient should not have received more than 1 prior line of chemotherapy (could have received immunotherapy which does not count as chemotherapy).
• ECOG PS 0-1
• Measurable disease as per RECIST v1.1. Subjects may have bone-only disease. NOTE: Bone-only subjects are eligible if their disease can be documented/evaluated by bone scans, CT or MRI. Their disease will be assessed using MD Anderson criteria. NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation.

• Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements:

  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Platelet count ≥ 100,000/mm3
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN). For subjects with Gilbert's Disease, total bilirubin ≤ 3 x ULN
  • ALT and AST ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5×ULN
  • International Normalized Ratio (INR) ≤1.5, if not therapeutically anticoagulated. Subjects who are being therapeutically anticoagulated may be included provided that the anticoagulation regimen is stable and closely monitored.
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m2 as determined using the Cockcroft-Gault formula.
• Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
• Male and female subjects of child- bearing potential must agree to use an effective method of birth control from the screening visit through 6 months after the last dose of study drug.

Exclusion Criteria:

• Platinum refractory disease defined as disease progression during first line platinum containing chemotherapy regimen. Progression following platinum based therapy is allowed.
• Prior therapy with a hypomethylating agent.
• Previously untreated (non-irradiated), symptomatic brain metastases. No prior treatment is required for non-symptomatic brain metastases. Previously treated symptomatic brain metastases are permitted.
• Unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
• Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy. (Suppressive therapy for chronic infections allowed, for example: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed. Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.)
• Hypersensitivity to (IMP) or components of the study treatment regimen.
• Treated with any investigational drug within 3 weeks of first dose of study treatment.
• Pregnant or breastfeeding.
• Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.