Combining ICI With SBRT or HypoFrx-RT for ES NSCLC

Patients will be assigned to Cohort A or Cohort B based on tumor stage (AJCC 8th Ed.). Cohort A: cT1-T3, N0, M0 (selected cT1, No, M0) Cohort B: cT4, N0, M0; cT1-4, N1-3, M0 Phase I: This portion of the study will utilize a standard 3 + 3 phase I design with three patients enrolled per radiation dose level in each cohort. Enrollment in the two cohorts is independent from one another. In both cohorts, an anti-PD-(L)1 immune checkpoint inhibitor will be given concurrently and adjuvantly with radiotherapy for approximately 1 year. The radiation dose escalation for each cohort is listed below: Cohort A (SBRT): (Optional): 8 Gy x 5 daily fractions Level 1: 9 Gy x 5 daily fractions Level 2: 10 Gy x 5 daily fractions Level 3: 11 Gy x 5 daily fractions Cohort B (HypoFrx-RT): (Optional): 3 Gy x 15 daily fractions Level 1: 3.5 Gy x 15 daily fractions Level 2: 4 Gy x 15 daily fractions DLTs will be based on events occurring during the course of radiotherapy. Concurrent administration of an immune checkpoint inhibitor is defined as: An anti-PD-(L)1 immune checkpoint inhibitor administered with standard dosing (Durvalumab: 1500 mg every 4 weeks) given within 5 days prior to the beginning of radiotherapy. Adjuvant administration of an immune checkpoint inhibitor is defined as: An anti-PD-(L)1 immune checkpoint inhibitor administered with standard dosing (Durvalumab: 1500 mg every 4 weeks) for approximately 1 year or until progression or other discontinuation criteria are met. Phase II: Once a maximum tolerated dose (MTD) is defined in each cohort, this dose will be used as the only radiation dose in each corresponding cohort in the phase II portion of this study. Dosing regimen of the immune checkpoint inhibitor will remain the same as that used in the phase I portion of this study. For this protocol, patients will be followed up to 2 years after the last dose of immune checkpoint inhibitor is administered.