A Randomized Phase II/III Trial of Modern Immunotherapy Based Systemic Therapy with or without SBRT for PD-L1 Negative, Advanced Non-Small Cell Lung Cancer

Protocol: Alliance – A082002

SCHEMA A082002

Please Note: Below is partial eligibility, for full eligibility requirements, please contact the Genesys Hurley Cancer Institute Research Department at (810)762-8181, (810)762-8079 and/or (810)762-8038. Thank you!

Eligibility:

1. Histologic or cytologic diagnosis of Stage IV NSCLC using version AJCC 8th edition (includes M1a, M1b, and M1c stage disease). Patients with Stage IIIB and IIIC disease are eligible if they are not a candidate for combined chemotherapy and radiation. PD-L1 IHC: PD-L1 expression Tumor Proportion Score (TPS) <1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed patients are not eligible. The assay must have been performed locally by a CLIA (or equivalent) certified laboratory. For non-squamous patients only (adenocarcinoma or adenosquamous): EGFR, ALK and ROS1 testing must be done locally. No patients with known
   actionable EGFR mutations (except exon 20 insertion), ALK or ROS1 mutations that can be treated with oral tyrosine inhibitors.
2. Measurable disease, including at least two cancerous deposits. At least one deposit must be RECIST measurable (and not to be irradiated) while at least one OTHER deposit (measurable or non-measurable) must meet criteria for SBRT
3. Age ≥ 18 years.
4. ECOG Performance Status 0-2.
5. No prior systemic chemotherapy or immunotherapy for advanced NSCLC. No prior treatment with checkpoint inhibitors for metastatic lung cancer. Chemotherapy for non-metastatic disease (e.g., adjuvant therapy) or
   immunotherapy for locally advanced Stage III disease is allowed if terminated at least 6 months prior to registration.No systemic immunostimulatory or immunosuppressive drugs, including >10mg prednisone equivalent per day, within 2 weeks or 5 half-live of the drug, whichever is shorter. ≥ 1 week since palliative (including CNS) radiotherapy to any tumor site. No prior allogeneic tissue/solid organ transplant.
6. No uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study
   requirements. No active auto-immune disease that requires systemic therapy within 2 years prior to registration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
7. No patients with a “currently active” second malignancy that is progressing or has required active treatment within the last 2 years. Participants with nonmelanoma skin cancers or carcinoma in-situ (e.g., breast carcinoma, urothelial carcinomaor cervical cancer in situ) or localized prostate cancer (T1-3, N0, M0) that have undergone potentially curative therapy are eligible.
8. No hypersensitivity (≥ Grade 3) to immunotherapy and/or any of its
   excipients.