This is a single center pilot, phase Ib study with a safety lead-in evaluating the safety and preliminary efficacy of the EBP inhibitor DSP-0390 in combination with atezolizumab in patients with extensive stage small cell lung cancer (ES-SCLC) whose disease has not progressed after initial induction therapy with platinum-based chemotherapy and anti-PD-L1 immunotherapy (atezolizumab or durvalumab per treating physician's discretion). This trial is testing the hypothesis that inhibition of de novo cholesterol synthesis by DSP-0390 when used in combination with atezolizumab in the maintenance therapy of patients with ES-SCLC will be tolerable.

Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer.

• Completed 3-4 cycles of induction chemoimmunotherapy as first line treatment of ES-SCLC without disease progression.

• Measurable disease per RECIST 1.1.

• At least 18 years of age.

• ECOG performance status ≤ 2

• Adequate bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1.0 K/cumm
  • Platelets ≥ 100 K/cumm
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN (≤ 5.0 x IULN for patients with liver metastases)
  • Calculated creatinine clearance > 40 mL/min by Cockcroft-Gault

• The effects of DSP-0390 on the developing human fetus are unknown. For this reason, people of childbearing potential and people able to father a child must agree to use adequate contraception prior to study entry, for the duration of study treatment, and for 6 months after the last dose of DSP-0390.

• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition (following discussion with the PI) are eligible for this trial
• Currently receiving any other investigational agents, or received within 4 weeks prior to Day 1 (unless investigational immunotherapy, which may not have been received within 6 weeks prior to Day 1).
• Patients with untreated symptomatic brain metastases or with clinically evident CNS hemorrhage. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression. Patients with asymptomatic, punctate brain metastases < 5 mm are allowed.
• Known contraindications to use of PD-L1 inhibitor as assessed by the treating physician.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DSP-0390 or atezolizumab.
• Undergone major surgery within 28 days prior to Cycle 1 Day 1.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to Cycle 1 Day 1.
• Patient is known to have short-gut syndrome, or other condition that may significantly limit the ingestion or gastrointestinal absorption of drugs administered orally.
• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
• Concurrent use of prohibited medications: carbamazepine, phenytoin, phenobarbital, other strong or moderate CYP3A4 inhibitor or inducer, or strong CYP2D6 inhibitors. These should be discontinued 1 week or 5 half-lives (whichever is greater) prior to study day 1. Note that both oral and IV ondansetron at doses ≤ 8 mg Q6h are permitted.
• Patient has a clinically significant abnormal ECG, including those where QT prolongation is determined by the Fridericia formula (QTcF >450 msec for males and >470 msec for females); and/or the patient has a history of Torsade de Pointes.