Venetoclax and Irinotecan for the Treatment of Relapsed or Refractory Small Cell Lung Cancer

Inclusion Criteria

• Histological or cytological diagnosis of SCLC
• Disease progression or recurrence during or after platinum-based therapy, unless platinum-based therapy was contraindicated
• Phase 1: Measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• Phase 2: Measurable disease according to RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 8.0 g/dL
• Serum creatinine =< upper limit of normal (ULN) for the lab or a calculated creatinine clearance >= 40 mL/min
• Total bilirubin =< 1.5 x ULN for the laboratory
• Aspartate aminotransferase (AST) =< 2.5 x ULN for the laboratory
• Alanine aminotransferase (ALT) =< 2.5 x ULN for the laboratory
• Persons with known human immunodeficiency virus (HIV) seropositivity are eligible if they meet the following criteria: * CD4 count >= 200/mm^3 * Undetectable HIV viral load on standard polymerase chain reaction (PCR)-based test * On a stable regimen of highly active anti-retroviral therapy (HAART) that does not include protocol contraindicated agents * No ongoing requirement for concurrent antibiotics or antifungal agents for the prevention of HIV-associated opportunistic infections
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Ongoing requirement for any non-study anticancer therapy
• Ongoing or planned treatment with any of the following: * Greater than 10 mg prednisone daily or equivalent * Immunosuppressive agents * Strong or moderate CYP3A inhibitor or inducer, or a narrow-therapeutic sensitive substrate * P-glycoprotein (gp) inhibitor or narrow-therapeutic sensitive P-gp substrate If any of these agents have been used, patients must be off them for >= 1 week before initiation of study treatment
• Any investigational agent within 21 days prior to the first dose of the investigational drugs
• Has consumed grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days before initiation of study treatment
• Phase 2 portion only: Previous systemic anticancer therapy other than platinumbased therapy
• Known leptomeningeal metastases
• Known untreated brain metastases
• Brain metastases that have been treated and demonstrate progression on posttreatment imaging
• Hypersensitivity to irinotecan, venetoclax, or their excipients
• Diarrhea >= grade 1
• Ongoing need for antidiarrheal agents
• Active uncontrolled infection, ongoing or within 2 weeks before initiating treatment
• Known homozygosity for the UGT1A1*28 allele * Note: Study-specific UGT1A1 testing is not required
• Inability to swallow oral medications and/or malabsorption
• Pregnancy or breastfeeding
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient’s risk or limit the patient’s adherence with study requirements