Study of Bevacizumab in Combination With Chemoimmunotherapy and Atezolizumab in Patients With Extensive Stage Small Cell Lung Cancer and Liver Metastases

Ability for subject to sign informed consent form and ability for subject to comply with the requirements of the study.

Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group staging system), and radiographic confirmation of LM at diagnosis.

Patients with history of EGFR mutant non-small cell lung cancer with histologically confirmed transformation to small cell lung cancer with presence of liver metastases, who are chemotherapy and immunotherapy naïve are eligible.

No prior treatment for ES-SCLC. Note: patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least six months since the last chemotherapy, radiotherapy or chemoradiotherapy cycle prior to diagnosis of ES-SCLC

Measurable disease per RECIST v1.1

* Metastases are limited to the cerebellum or supratentorial region (i.e., no metastases to the midbrain, pons, or medulla).

* Presence of measurable disease outside the CNS per RECIST v1.1.

* No history of intracranial hemorrhage or spinal cord hemorrhage.

* No stereotactic radiotherapy or whole brain radiotherapy within 14 days prior to initiation of study treatment or neurosurgical resection within 28 days prior to initiation of study treatment.

* Concurrent therapy of corticosteroids ≤ 10 mg of oral prednisone or equivalent and/or anticonvulsant therapy at stable dose.

ECOG Performance Status of 0-2.

Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:

* Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 45 mL/min (calculated using the Cockcroft-Gault formula)

* ANC ≥1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor support

* Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion

* AST, ALT, and alkaline phosphatase (ALP) ≤ 5 x upper limit of normal (ULN), and serum bilirubin ≤ 1.5 x ULN

* For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN

* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

For patients who have positive hepatitis C antibody, HCV RNA must be performed at screening. For patients with a positive hepatitis C antibody with prior treatment or natural resolution who have negative HCV RNA are eligible. Patients with untreated hepatitis C may enroll if hepatitis is stable, and the patient is not at risk for hepatic decompensation. For those on concurrent HCV treatment, the HCV RNA level should be below the limit of quantification.

Negative serum pregnancy test for women of childbearing potential.

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, as defined below:

* Women must remain abstinent or use an acceptable contraceptive method during the treatment period and for 5 months after the final dose of atezolizumab and 6 months after the final dose of bevacizumab.

* A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.

* Examples of acceptable contraceptive methods include, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.

For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:

* With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during treatment with chemotherapy (i.e., carboplatin and etoposide) and for at least 6 months after the final dose of chemotherapy, atezolizumab and bevacizumab to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of preventing drug exposure.

Known chronic hepatitis B

Live, attenuated vaccines (e.g., FluMist®) are prohibited within 4 weeks prior to initiation of study treatment, during treatment with atezolizumab, and for 5 months after the last dose of atezolizumab.

Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNFα agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:

* Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after confirmation with the Principal Investigator has been obtained.

* Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.

History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation

Known allergy or hypersensitivity to any component of the bevacizumab formulation

Currently taking or plan to take traditional herbal medicines.

Treatment with investigational therapy within 28 days prior to initiation of study treatment

Study of Bevacizumab in Combination With Chemoimmunotherapy and Atezolizumab in Patients With Extensive Stage Small Cell Lung Cancer and Liver Metastases

What this study is about

Study of Bevacizumab in Combination With Chemoimmunotherapy and Atezolizumab in Patients With Extensive Stage Small Cell Lung Cancer and Liver Metastases

What this study is about