Concomitant Radiotherapy, Tremelimumab & Durvalumab for Advanced NSCLC Patients Progressing on First-line Immunotherapy

This is an open-label, single-arm, phase 2a trial with a safety run-in cohort followed by a Simon two-step design expansion cohort, of two checkpoint blockage treatments and radiotherapy in the treatment of locally advanced or metastatic NSCLC who have failed first-line immunotherapy (alone or as a combination regimen with chemotherapy). Study objectives: Objective of the safety run-in phase: • To evaluate safety of the triple combination of irradiation -Durvalumab - Tremelimumab Co-Primary objectives of the entire study: * To evaluate safety of the triple combination (as for the run-in phase). * To evaluate response rate on study drug compared to historical data of response to first-line platinum-doublet chemotherapy and 2nd-line docetaxel. Secondary objective: • To evaluate PFS and OS compared to historical data . Exploratory objectives: * Examine the mechanism of resistance to first-line immunotherapy . * Examine the immune response in irradiation -Durvalumab - Tremelimumab treated patients and identify potential predictors of clinical benefit.

NCT Number	NCT05000710
Lead Sponsor	Sheba Medical Center Collaborators: AstraZeneca, Rambam Health Care Campus, Tel-Aviv Sourasky Medical Center
Conditions	Metastatic or Locally Advanced NSCLC
Enrollment	29 participants
Start Date	2021-12-09
Primary Completion	2026-12 (estimated)
Study Completion	2026-12 (estimated)
Updated on ClinicalTrials.gov	2024-12-05