Chemotherapy and Atezolizumab for Patients With Extensive Stage Small Cell Lung Cancer (SCLC) With Untreated, Asymptomatic Brain Metastases

Inclusion Criteria:

1. Written informed consent and HIPAA authorization for release of personal healthinformation prior to registration. NOTE: HIPAA authorization may be included in theinformed consent or obtained separately.
2. Age ≥ 18 years with ability and willingness to provide informed consent.
3. ECOG Performance Status of 0-2.
4. Histological confirmation of Small Cell Lung Cancer- Extensive Stage (SCLC) perVeterans Administration Lung Study Group (VALG).
5. At least one untreated asymptomatic brain metastasis that is measurable by RECIST 1.1that has not been previously irradiated.
6. No prior treatment for metastatic disease. EXCEPTION: A single cycle of chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30 days prior toenrollment.
7. Treatment-free for at least 6 months since last chemo/radiotherapy, among thosetreated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC.
8. Any prior cancer treatment must be completed at least 6 months prior to registrationand the subject must have recovered from all reversible acute toxic effects of theregimen (other than alopecia) to Grade ≤ 1 or baseline. NOTE: a single cycle ofchemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30days prior to enrollment. NOTE: Extracranial radiation is allowed.
9. A concurrent diagnosis of a separate malignancy is allowed if clinically stable anddoes not require tumor-directed therapy.
10. Demonstrate adequate organ function as defined in the table below

• Absolute Neutrophil Count (ANC) ≥ 1.5K/mm3 without GCSF
• Hemoglobin (Hgb) ≥ 9 g/dL (without transfusion)
• Lymphocyte Count: ≥ 500/µL
• Platelet Count: ≥ 100,000/µL without transfusion
• Calculated creatinine clearance ≥ 50 cc/min OR Serum Cr < 1.5 x institutional ULN
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2 × ULN without liver metastasis ≤ 5 × ULNwith liver metastasis
• Alanine aminotransferase (ALT) ≤ 2 × ULN without liver metastasis ≤ 5 × ULN withliver metastasis

11. Females of childbearing potential must have a negative serum pregnancy test within 3days (72 hours) prior to enrollment. NOTE: Females are considered of childbearingpotential unless they are surgically sterile (have undergone a hysterectomy orbilateral oophorectomy) or they are naturally postmenopausal for at least 12consecutive months.
12. Females of childbearing potential and males must be willing to abstain fromheterosexual activity or to use 2 forms of effective methods of contraception,including at least one method with a failure of < 1% per year, from the time ofinformed consent until 150 days (5 months) after treatment discontinuation.
13. Negative hepatitis B surface antigen (HBsAg) test, negative total hepatitis B coreantibody (HBcAb) test, or positive total HBcAb test followed by a negative hepatitis Bvirus (HBV) DNA test. The HBV DNA test will be performed only for patients who have apositive total HBcAb test. Testing required at screening only if results are notknown.
14. Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followedby a negative HCV RNA test. The HCV RNA test will be performed only for patients whohave a positive HCV antibody test. A positive HCV RNA test is sufficient to diagnoseactive HCV infection in the absence of an HCV antibody test.
15. As determined by the enrolling physician or protocol designee, ability of the subjectto understand and comply with study procedures.

Exclusion Criteria:

1. Known active CNS metastases which are symptomatic. CNS metastases are consideredasymptomatic if the patient does not require high dose or escalating corticosteroidsor anticonvulsant therapy. Steroid dose must be equivalent to 2 mg of dexamethasone orless daily.

• Prior steroid use as part of an anti-emetic regimen with chemotherapy is allowed.
• Patients must be on a stable dose of corticosteroid. No tapering or decreasingdose within 7 days of enrollment.

2. Leptomeningeal disease. Discrete dural-based metastases will be allowed withoutevidence of leptomeningeal disease.
3. Radiation therapy within 14 days prior to Day 1 of Cycle 1 Day 1. NOTE: Extracranialradiation is allowed.
4. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12mg/dL or corrected serum calcium > ULN)
5. Known auto-immune conditions requiring systemic immune suppression therapy other thanprednisone < 10 mg daily (or equivalent).
6. History of interstitial pneumonitis from any cause.
7. Concurrent severe and/or uncontrolled medical conditions which may compromiseparticipation in the study as assessed by site investigator.
8. Current active infectious disease requiring systemic antibiotics, antifungal, orantiviral treatment on Cycle 1 Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonarydisease) are eligible. NOTE: Subjects with active tuberculosis are NOT eligible.
9. Current use of medications specified by the protocol as prohibited for administrationin combination with the study drugs. This includes patients with a condition requiringsystemic treatment with either corticosteroids (>10 mg daily prednisone equivalents)or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1. Inhaledor topical steroids and adrenal replacement doses >10 mg daily prednisone equivalentsare permitted in the absence of active autoimmune disease. Patients who are receivingdenosumab prior to enrollment must be willing and eligible to receive a bisphosphonateinstead.
10. History of myocardial infarction, NYHA class II or greater congestive heart failure,or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment.
11. Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), Testing not required at screening.
12. Requirement for ongoing anticoagulation with heparin, low molecular weight heparin, orother oral anticoagulant (coumadin, DOAC).
13. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrentdrainage procedures (once monthly or more frequently). NOTE: Patients with indwellingcatheters (e.g., PleurX®) are allowed.
14. History of severe allergic, anaphylactic, or other hypersensitivity reactions tochimeric or humanized antibodies or fusion proteins.
15. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamsterovary cells or any component of the atezolizumab formulation.
16. History of allergic reactions to carboplatin or etoposide.
17. Intolerance of atezolizumab or other PD-1/PD-L1 axis drug(s), or any other antibody ordrug specifically targeting T-cell co-stimulation or immune checkpoint pathways,including prior therapy with anti-tumor vaccines or other immune-stimulatoryanti-tumor agents.
18. Active or history of autoimmune disease or immune deficiency, including, but notlimited to, myasthenia gravis, myositis, autoimmune hepatitis, inflammatory boweldisease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome,Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

• Patients with a history of autoimmune-related hypothyroidism who are onthyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimenare eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo withdermatologic manifestations only (e.g., patients with psoriatic arthritis areexcluded) are eligible for the study provided all of following conditions aremet:
• Rash must cover < 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topicalcorticosteroids
• There has been no occurrence of acute exacerbations of the underlyingcondition requiring psoralen plus ultraviolet A radiation, methotrexate,retinoids, biologic agents, oral calcineurin inhibitors

19. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of studytreatment, or anticipation of need for such a vaccine during atezolizumab treatment orwithin 5 months after the final dose of atezolizumab.
20. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while themother is being treated on study).
21. Treatment with any investigational drug within 28 days prior to Cycle 1 Day 1.