S1914 - A Randomized Phase III Trial Of Induction/Consolidation Atezolizumab + Sbrt Versus Sbrt Alone In High Risk, Early Stage NSCLC

The purpose of this study is compare overall survival (OS) in participants with inoperable, early stage non-small cell lung cancer (NSCLC) randomized to stereotactic body radiation therapy (SBRT) with or without atezolizumab.

This study will also compare investigator-assessed progression-free survival (IA-PFS) between the arms, and compare PFS by blinded independent centralized review (BIRC) between the arms in a random subset of participants. The study also hopes to evaluate distant, locoregional, and local failure rates within each treatment arm and to assess quality of life as measured by the EORTC QLQ-30 and EORTC-QLQ-LC13 survey.

This study has public funding from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) in the United States Department of Health and Human Services.

Inova Schar Cancer Institute
A department of Inova Fairfax Hospital
8081 Innovation Park Dr.
Fairfax, VA 22031

• Age 18 years or older
• Participant must have histologically or cytologically proven Stage I-IIA or limited T3N0M0 non-small cell lung cancer (NSCLC) as defined in Section 4.0, without radiographic evidence of nodal or distant involvement (N0M0). Participant may have T3 disease with the exclusion of pericardial involvement. Participants with multifocal tumors with no more than two lesions confirmed or suspected to be synchronous early stage NSCLCs are eligible provided at least one lesion is histologically or cytologically proven to be NSCLC and meets one or more high-risk features
  • Tumor diameter ≥ 2 cm (inclusive of any non-solid, ground glass component) as assessed by diagnostic CT
  • Tumor SUV max ≥ 6.2 as assessed by FDG PET/CT
  • Moderately differentiated, poorly differentiated, or undifferentiated histology
• Participant must have undergone diagnostic chest CT with or without contrast (IV contrast preferred) within 42 days prior to randomization. PET-CT may be used if the CT portion is of comparable diagnostic quality to a stand-alone CT. All disease must be assessed within 42 days prior to randomization.
• Participant must have undergone FDG PET/CT of chest within 90 days prior to randomization
• Participant must not have evidence of hilar or mediastinal nodal involvement. Any participant with radiographically suspicious hilar or mediastinal nodes (including features such as non-calcified nodes with a short axis diameter > 1 cm, abnormal morphology, and/or elevated FDG avidity) must undergo cytologic sampling of suspicious nodes to rule out involvement prior to randomization. Mediastinal nodal sampling for other participants is optional
• Participant must be medically or surgically inoperable as documented by a board certified thoracic surgeon or multi-disciplinary tumor board consensus OR participant’s unwillingness to undergo surgical resection must be clearly documented
• Additional eligibility in protocol

• Pregnancy/breastfeeding
• Participants must not have a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric antibodies, fusion proteins, or Chinese hamster ovary cell products or to any component of the atezolizumab formulation) or use contraceptive methods, and agreement to refrain from donating sperm
• Prior systemic treatment for metastatic non-squamous NSCLC
• Participant must not have received any prior treatment for the current NSCLC diagnosis
• Participant must not have undergone prior radiation to overlapping regions of the chest that, in the opinion of the treatment physician, will interfere with protocol treatment
• Participant must not have significant cardiovascular disease
• Participant must not have myocardial infarction within 90 days prior to randomization
• Participant must not have unstable arrhythmias or unstable angina
• Participant must not have known left ventricular ejection fraction (LVEF) <40% within 28 days prior to randomization
• Participant must not have an active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Participants must not have a prior or concurrent malignancy whose natural history or treatment has the potential (in the opinion of the treating physician) to interfere with the safety or efficacy assessment of the investigational regimen
• Additional ineligibility in protocol

For additional information, please go to: https://clinicaltrials.gov/ct2/show/NCT04214262