Bomedemstat and Maintenance Immunotherapy for Treatment of Newly Diagnosed Extensive Stage Small Cell Lung Cancer

Inclusion Criteria:

• Adult aged 18 years or older and willing and able to provide written informedconsent

• Histologically confirmed diagnosis of extensive stage small-cell lung cancer (ES-SCLC)

• Note: Previously treated limited stage SCLC (LS-SCLC) patients are eligible ifdisease progression had occurred following completion of definitive treatmentfor LS-SCLC. Determination of disease progression after prior therapy forLS-SCLC is at the discretion of the investigator

• Having received four cycles of platinum-etoposide concurrent with three or fourcycles of immune checkpoint inhibitor as induction systemic therapy for ES-SCLCimmediately prior to study enrollment (see below for definitions). Note that immunecheckpoint inhibitor may have been omitted from the first cycle only

• Platinum is defined as cisplatin or carboplatin. Immune checkpoint inhibitor isdefined as atezolizumab, durvalumab, or other anti-PDL1 or anti-PD1 monoclonalantibody that is approved by the United States (US) Food and DrugAdministration for first-line treatment of ES-SCLC in combination with platinumand etoposide at the time of treatment receipt. Immediately prior is defined asreceipt of cycle 1 day 1 of platinum-etoposide +/- immune checkpoint inhibitorno more than 112 days prior to cycle 1 day 1 of study treatment, andadministration of fourth cycle of platinum-etoposide and immune checkpointinhibitor no more than 30 days prior to cycle 1 day 1 of study treatment

• Eligible to receive maintenance atezolizumab, as defined by stable disease orbetter, following induction platinum-etoposide and immune checkpoint inhibitor.Determination of response to induction therapy is at the discretion of theinvestigator. Investigators should contact the principal investigator (PI) ifclarification is needed

• Eastern Cooperative Oncology Group (ECOG performance status of =< 2)

• Minimum life expectancy of >= 12 weeks

• Note: myeloid growth factor use within 14 days of study treatment initiation isnot permitted. Growth factor may have been previously administered duringinduction chemoimmunotherapy

• Platelet count (Plt) >= 75 x 10^3/mcL (without transfusion)

• Hemoglobin (Hgb) >= 8.0 g/dL (transfusion is permitted)

• Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) >= 40 mL/min or serum creatinine =< 1.5 x upper limit of normal

• Serum total bilirubin =< 1.5 x upper limit of normal (ULN) or =< 3 x ULN forsubjects with Gilbert's disease

• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 xULN (=< 5 x ULN if evidence of hepatic involvement by malignant disease)

• International normalized ratio (INR) < 1.5 x upper limit of normal (only in patientsnot receiving anticoagulant agents at baseline)

• Note: there is no INR or activated partial thromboplastin time (aPTT) thresholdfor patients who are receiving anticoagulant agents at baseline, but patientsmust be on a stable dose of anticoagulant, and discontinuation of allanticoagulation while the platelet count is below 50 x 10^3/mcL must be deemedappropriate for the patient by the investigator prior to enrollment

• Activated partial thromboplastin time (aPTT) < 1.5 x the local upper limit of normal (only in patients not receiving anticoagulant agents at baseline)

• Note: there is no INR or aPTT threshold for patients who are receivinganticoagulant agents at baseline, but patients must be on a stable dose ofanticoagulant, and discontinuation of all anticoagulation while the plateletcount is below 50 x 10^3/mcL must be deemed appropriate for the patient by theinvestigator prior to enrollment

• Able to swallow capsules

• Amenable to peripheral blood sampling during the study

• Female subjects of childbearing potential should be willing to use 2 methods ofbirth control or abstain from heterosexual activity for the course of the studythrough 28 days after the last dose of study medication. Subjects of childbearingpotential are those who have not been surgically sterilized or have not been freefrom menses for > 1 year

• Male subjects who are sexually active with female partner(s) of childbearingpotential should be willing to use an adequate method of contraception starting withthe first dose of study therapy through 28 days after the last dose of study therapy

Exclusion Criteria:

• Prior receipt of systemic therapy for ES-SCLC other than four cycles of inductionplatinum-etoposide and immune checkpoint inhibitor

• Diagnosis of LS-SCLC that has not been previously treated

• Receipt of radiation therapy for symptomatic deterioration and/or radiographicdisease progression that was administered after initiation of inductionplatinum-etoposide and immune checkpoint inhibitor. Note: the presence of untreatedasymptomatic brain metastasis, or a history of receipt of radiation to brainmetastasis that was not initiated in response to symptomatic deterioration and/orradiographic disease progression following initiation of induction systemic therapy,does not preclude study participation. Investigators should contact the PI ifclarification is needed

• Anticipated use of prophylactic cranial irradiation or consolidative thoracicradiation therapy during study participation. Note: Palliative radiation to thecentral nervous system (CNS) for new CNS disease that develops during studyparticipation is allowed

• History of prior immune-related adverse event or other toxicity associated withimmune checkpoint inhibitor that precludes safe administration of maintenanceatezolizumab, in the opinion of the investigator

• Current or prior use of immunosuppressive medication within 14 days prior to thefirst dose of study treatment. The following are exceptions to this criterion:

• Intranasal, inhaled, topical steroids or local steroid injections (e.g.,intra-articular injection)

• Systemic corticosteroids at doses not to exceed 10 mg/d of prednisone orequivalent

• Steroids as premedication for hypersensitivity reactions (e.g., computedtomography [CT] scan premedication)

• Active autoimmune disease requiring systemic immunosuppression or history ofautoimmune disease requiring systemic immunosuppression within the last 2 years

• Note: Systemic immunosuppression should be interpreted as systemicglucocorticoids at a dose of greater than 10 mg/day of prednisone orequivalent, systemic biologic agents including monoclonal antibodies againstinflammatory mediators, or small molecule agents. Investigators should contactthe PI if clarification is needed

• Active pneumonitis or interstitial lung disease (ILD), or a history ofpneumonitis/ILD, which required systemic immunosuppression (e.g. corticosteroids)

• Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, hemophilia,Von Willebrand's disease, disseminated intravascular coagulation [DIC], fibrinogendeficiency, or other clotting factor deficiency), at the discretion of theinvestigator

• History of severe thrombocytopenia or platelet dysfunction (e.g. immunethrombocytopenic purpura), at the discretion of the investigator

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugschemically related to bomedemstat or LSD1 inhibitors (i.e., monoamine oxidaseinhibitors; MAOIs) that contraindicates their participation

• Any hypersensitivity to PD-1/PD-L1 targeting agents

• Current use of monoamine oxidase A and B inhibitors (MAOIs)

• Current use of a prohibited medication (e.g. romiplostim) or expected to require anyof these medications during treatment with the investigational drug

• Current or anticipated use of an antiplatelet (e.g. clopidogrel), anticoagulant (e.g. warfarin or apixaban), or nonsteroidal anti-inflammatory drug (NSAID) withantiplatelet activity (e.g. aspirin, ibuprofen), that, in the opinion of theinvestigator, could NOT be safely discontinued when the subject's platelet countdecreases below 50 x 10^3/mcL

• Has undergone major surgery within 4 weeks prior to starting study drug and/or hasnot recovered from side effects of such surgery. Note: Major surgery and recoveryare defined at the discretion of the investigator

• Receipt of a live vaccine within 30 days of first dose of study therapy

• Uncontrolled active infection

• Any concomitant active malignancy considered clinically significant by theinvestigator

• Known human immunodeficiency virus (HIV) infection or known active hepatitis B orhepatitis C virus infection (testing will not be conducted as part of screeningprocedures)

• History of any illness/impairment of gastrointestinal (GI) function that mightinterfere with drug absorption (e.g. chronic diarrhea), confound the study resultsor pose an additional risk to the patient by participation in the study

• Use of an investigational agent within 28 days, or the equivalent of at least 7half-lives of that agent, whichever is the shorter, prior to the study day 1

• Females who are pregnant or breastfeeding or plan to become pregnant or breastfeedat any time during the study