LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer

Inclusion Criteria:

Histologically or cytologically confirmed extensive-stage disease small cell lung carcinoma per the Veterans Administration Lung Study Group (VALG) staging system
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST): Revised RECIST guideline (version 1.1)
Estimated life expectancy of at least 12 weeks
For women: Must be surgically sterile (surgical procedure: bilateral tubal ligation), post-menopausal (at least 12 consecutive months of amenorrhea) or have a negative pregnancy test. Women of childbearing potential must be compliant with a medically approved contraceptive regimen (intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test within 14 days before study drug treatment and must not be breastfeeding

For men: agreement to remain abstinent or use medically approved contraceptive measures, as defined below:

With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during study therapy and for at least 6 months after the last dose of study therapy to avoid exposing the embryo
A performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale
Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 10/L
Platelets >= 100 x 10/L
Hemoglobin >= 9 g/dL
Bilirubin =< 1.5 times upper limits of normal (ULN) may be enrolled
Alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 times ULN (AP, AST, and ALT =< 5 times ULN are acceptable if the liver has tumor involvement)
Calculated creatinine clearance (CrCl) >= 60 mL/min based on the Cockcroft and Gault formula
All subjects must have the ability to understand and the willingness to sign a written informed consent
No prior systemic chemotherapy, immunotherapy, biological, hormonal, or investigational therapy for SCLC

Exclusion Criteria:

Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Diagnosis of non-small cell lung cancer (NSCLC) or mixed NSCLC and small cell lung cancer (SCLC)
No prior malignancy other than SCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more years prior to study entry with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score =< 6 = Gleason group 1) localized prostate cancer will be eligible even if diagnosed less than 5 years prior to study entry
Serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol
Active or ongoing infection during screening requiring the use of systemic antibiotics
Serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease as defined by the New York Heart Association class III or IV
Clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug
Known or suspected allergy to any agent given in association with this trial
Pregnant or lactating women
History of autoimmune disease, including minor/mild autoimmune disease not requiring immunosuppressants (such as eczema on less than 10% of the body surface area and long term diabetes mellitus type 1 on stable insulin)
Known hepatitis B or hepatitis C
Known human immunodeficiency virus (HIV) positive
Treatment with systemic corticosteroid or other immunosuppressive medication. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed
Administration of a live, attenuated vaccine within 28 days prior to study
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters are allowed
Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN). Patients who are receiving denosumab prior to study entry must be willing and eligible to discontinue its use and replace it with a bisphosphonate while in the study
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
Prior allogeneic bone marrow transplantation or solid organ transplant
QTcF (Fridericia Correction Formula) > 470 on 2 out of 3 electrocardiograms (EKG's)
Diagnosis of congenital long QT syndrome
Treatment, within 7 days prior to first dose of study drug, with medications that are known to prolong the QT interval and/or are associated with a risk of torsades de pointes
Treatment with CYP450 substrates within 7 days prior to first dose of study drug
Treatment with nephrotoxic compounds within 7 days prior to first dose of study drug
Treatment with warfarin within 7 days prior to first dose of study drug
Treatment with antiepileptic medications that may increase etoposide clearance (including but not limited to phenytoin, phenobarbital, carbamazepine, and valproic acid) within 7 days prior to first dose of study drug
Treatment with strong P-glycoprotein inhibitors within 7 days prior to first dose of study drug
Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study