Venetoclax and Irinotecan in Relapsed/Refractory SCLC

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 RECIST v1.1 * Phase 2: Measurable disease according to RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Age ≥ 18 years * Adequate bone marrow function as defined below: * Absolute neutrophil count (ANC) ≥ 1,500/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 8.0 g/dL * Adequate renal function as defined below: * Serum creatinine ≤ upper limit of normal (ULN) for the lab or a calculated creatinine clearance ≥ 40 mL/min * Adequate hepatic function as defined below: * 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 HIV seropositivity are eligible if they meet the following criteria: * CD4 count ≥ 200/mm3 * Undetectable HIV viral load on standard 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-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 platinum-based therapy * Known leptomeningeal metastases * Known untreated brain metastases * 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