Safety and Biomarker Analysis of NRG-LU004: Phase I Trial of Accelerated or Conventionally Fractionated Radiotherapy Combined With Durvalumab in PD-L1 High Locally Advanced Non-Small Cell Lung Cancer
In brief
Only one dose-limiting toxicity among 24 patients receiving durvalumab with radiotherapy
In a phase I trial of 24 PD-L1 high locally advanced NSCLC patients, concurrent durvalumab and either accelerated (60 Gy/15 fractions) or standard (60 Gy/30 fractions) thoracic radiotherapy caused a single dose-limiting toxicity, meeting safety criteria. Feasibility was met in most patients, and blood profiling suggested immune changes, supporting a chemotherapy-free approach while highlighting the need for larger efficacy studies.
- Journal
- International journal of radiation oncology, biology, physics (Q1)
- Published
- 12 September 2026
- Study design
- Phase 1 (first-in-human) trial
- Evidence level
- Level 4, Very Low (CEBM 4)
- Authors
- Steven H Lin, Stephanie L Pugh, Diane Marie Del Valle, Vladimir Roudko, Martin J Edelman, Anthony J Doemer, et al.
- PMID
- 42731785
- DOI
- 10.1016/j.ijrobp.2026.08.075
Why clinicians should know about it
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (paper of the day, 16 September 2026): Phase I trial of RT + durvalumab in PD‑L1‑high NSCLC
Abstract
BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 (>50%) expression show improved outcomes with immune checkpoint inhibitors compared to chemotherapy. We hypothesized that concurrent durvalumab and radiotherapy (RT) without concurrent chemotherapy would be safe and feasible in patients with locally advanced NSCLC (LA-NSCLC). METHODS: Stage II-III LA-NSCLC patients with PD-L1 >50% received durvalumab (1500 mg Q4 weeks x 13 cycles) with either accelerated fractionated RT (ACRT, 60 Gy/15 fractions) or standard fractionated RT (SDRT, 60 Gy/30 fractions), as initial and expansion cohorts. Primary objective was safety assessed through dose-limiting toxicities (DLTs). Feasibility was defined as ≥80% of patients receiving ≥80% of planned durvalumab in the first eight weeks. Peripheral blood specimens were collected at baseline and throughout treatment for exploratory immune profiling analyses to evaluate biomarkers related to treatment and/or adverse events. RESULTS: Among 24 evaluable patients (n=12 each), one DLT occurred (SDRT arm). Both initial cohorts advanced to expansion. Most patients received RT per protocol (83%). At time of analysis, 24% had completed all durvalumab cycles. In ACRT, adverse events included four grade 3, one grade 4 (lymphopenia), and one grade 5 (lung infection, unrelated). In SDRT, there were eight grade 3 and one grade 5 (respiratory failure, unrelated) events reported. Durvalumab feasibility was 85% in ACRT and 75% in SDRT. RT was completed per protocol in all 12 ACRT, and 10 of 12 for SDRT. Soluble proteomic analysis revealed significant immune changes particularly in the SDRT arm and potential biomarkers of immune-related adverse events. CONCLUSIONS: Chemotherapy-free thoracic RT with either standard fractionated or accelerated courses with concurrent durvalumab is safe in PD-L1 high LA-NSCLC.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.