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The purpose of the study is to determine whether adding vorolanib to atezolizumab will improve the length of time that participants are cancer-free after receiving standard chemotherapy.

Inclusion Criteria:

• Histologically or cytologically confirmed extensive stage small cell lung cancer without prior specific systemic therapy aside from induction with platinum, etoposide, and atezolizumab. Measurable disease is not required for eligibility.

• Receipt of at least 3 cycles (and no more than 4 cycles) of platinum plus etoposide and atezolizumab during the induction phase, without tumor progression as determined by CT scan and brain MRI. Patients should be able to start the study treatment no more than 6 weeks from the last dose of induction chemo/immunotherapy. This period may be extended to 8 weeks in patients requiring brain radiotherapy after completion of induction chemo/immunotherapy for brain metastases.

• At least 18 years of age.

• ECOG performance status ≤ 1

• Normal bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1.5 K/cumm
  • Platelets ≥ 100 K/cumm
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (≤ 5 x IULN for patients with liver metastases)
  • Creatinine ≤ 1.5 x IULN OR measured or calculated creatinine clearance > 50 mL/min for patients with creatinine levels > 1.5 x IULN
  • Urine protein ≤ 1+ or urine protein to creatinine ratio ≤ 1; if UPC ratio is > 1 on urinalysis, then 24-hour urine collection for protein must be obtained and level must be < 1,000 mg for patient enrollment
  • aPTT and either INR or PT ≤ 1.5 x IULN unless participant is receiving anticoagulant therapy as long as PT or a PTT is within therapeutic range of intended use of anticoagulants.

• Patients receiving therapeutic non-Coumadin anticoagulation are eligible, provided they are on a stable dose (per investigator judgment) of anticoagulant.

• The effects of atezolizumab and vorolanib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 31 weeks after last dose of study treatment. Women must use birth control for at least 31 weeks after last dose of study treatment. Women must not be breastfeeding.

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria

• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
• Currently receiving any other investigational agents.
• Patients with untreated brain metastases are excluded. Patients with clinically evident CNS hemorrhage are excluded. Prophylactic cranial irradiation is not allowed. Patients with brain metastases treated with whole brain radiation therapy, radiosurgery, or surgery are eligible.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorolanib, atezolizumab, or other agents used in the study.
• Use of chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
• Systemic glucocorticoids with prednisone dose higher than 10 mg/day or equivalent.
• Arterial or venous thromboembolic event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment.
• Uncontrolled or poorly controlled hypertension with systolic blood pressure (BP)> 160 mmHg systolic or diastolic > 100 mmHg for > 3 weeks prior to C1D1), despite standard medical management.
• Gastrointestinal perforation, and/or fistula, or risk factors for perforation within 6 months prior to enrollment.
• Grade 3 or 4 gastrointestinal bleeding within 3 months prior to enrollment.
• History of active autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.
• Hemoptysis (defined as bright red blood or ≥ ½ teaspoon) within 28 days prior to Cycle 1 Day 1 or with radiographic evidence of intratumor cavitation or radiologically documented evidence of major blood vessel invasion or encasement by cancer.
• Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to Cycle 1 Day 1.
• Undergone major surgery within 28 days prior to Cycle 1 Day 1, or minor surgery/subcutaneous venous access device placement within 7 days prior to Cycle 1 Day 1, or has elective or planned major surgery to be performed during the course of the clinical trial.
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis at a level of Child-Pugh B or worse, cirrhosis (any degree) with a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis (defined as ascites from cirrhosis requiring diuretics or paracentesis), fatty liver, and inherited liver disease.
• Active tuberculosis.
• Administration of a live, attenuated influenza vaccine within 4 weeks before Cycle 1 Day 1 or at any time during the study.
• Severe infections within 2 weeks prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1 Day 1. Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• History of deep venous thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to Cycle 1 Day 1.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to C1D1.
• Active hepatitis B (chronic or acute) defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Note: Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test are eligible.
• Patients known to be HIV positive are ineligible.

Adverse events were collected from start of treatment through 90 days after end of treatment (median 165 days, full range 93-527 days). All-cause mortality was followed up to 3 years after discontinuation of study treatment (median 446 days, full range 93-1526 days).