Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in People With Relapsed/Refractory Small Cell Lung Cancer

Background: EP0057 (formerly CRLX101) consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or "nanoparticle drug conjugate" travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Olaparib is a drug that may stop cancer cells from repairing the deoxyribonucleic acid (DNA) damage caused by chemotherapy. Researchers want to see how safe it is to give EP0057 and olaparib together and to see how well the combination treats a specific type of lung cancer called small cell lung cancer (SCLC). Objectives: To test the safety and maximum dose of EP0057 and olaparib together. To test how well they treat small cell lung cancer. Eligibility: Adults 18 and older with small cell lung cancer. Design: Participants will be screened with standard cancer care tests. Participants will get the 2 study drugs in 28-day cycles. EP0057 will be given every 2 weeks, through a small plastic tube in an arm vein. Olaparib will be taken by mouth twice a day most days. Participants will keep a pill diary. For Cycle 1, participants will have 3 visits. All other cycles will have 2 visits. At study visits, participants may have: * Blood and hair samples taken * History and Physical exam * Questions about health and side effects * Pregnancy test * Optional tumor biopsy where a piece of tumor is removed by needle after numbing the skin. * Computed tomography (CT) scan * Injection of EP0057 (twice per cycle) * Olaparib prescription Participants will have a follow-up visit 4 weeks after finish taking the drugs. They will have a physical exam and blood tests. They may have a tumor biopsy. The study team will call the patient every 3 months for follow up after completing the study treatment.

* INCLUSION CRITERIA: - Phase I * Patients must have histologically or cytologically confirmed advanced solid tumor that is resistant or refractory to standard therapy. * A minimum of 2 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation. In addition, recovery to Grade \=1,500/mcL without growth factor support * platelets \>=100,000/mcL without growth factor support * hemoglobin \>=9 g/dL, and no blood transfusion within 4 weeks. OR * Hemoglobin \>10 g/dL, and no blood transfusion within 2 weeks. * total bilirubin \= 18 years of age. * Patient must have received at least one platinum-based regimen of chemotherapy and/or an immune-checkpoint inhibitor if appropriate with progressive disease. * Prior antiangiogenic and radiation therapy are permitted (2-week washout from therapy is required). * Bisphosphonates and denosumab are permitted if on a stable dose for \>=4 weeks. * ECOG 0-2 * Patients must have normal organ and marrow function as defined below: * leukocytes \>=3,000/mcL * absolute neutrophil count \>=1,500/mcL without growth factor support * platelets \>=100,000/mcL without growth * factor support * hemoglobin \>=9 g/dL, and no blood transfusion within 4 weeks. OR * hemoglobin \>10 g/dL, and no blood transfusion within 2 weeks. * total bilirubin\ \