949TiP Neoadjuvant durvalumab in non-surgical early stage/locally advanced non-small cell lung cancer (NSCLC) followed by radical RT/CRT (IDEAR) study concept of a phase II investigator initiated clinical trial

Abstract

Targeting the PD1/PD-L1 pathway has demonstrated activity in patients with advanced malignancies. Treatment with anti-PD1/PD-L1 blockade in advanced and locally advanced NSCLC, is already standard of care. The positive outcomes of durvalumab following CRT emphasized the potential of immunotherapy integration in multimodality treatment strategies and in earlier phases of the disease, leading to the first immune checkpoint inhibitor approval in non-metastatic setting in NSCLC. This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients with localized NSCLC who are planned to undergo radical RT or CRT. Main inclusion criteria: ≥ 18 y/o; histologically documented NSCLC; clinical Stage IIIA NSCLC eligible for RT or clinical stage IB (≥ 4 cm)-IIIA NSCLC that are not considered for surgical treatment by the clinical team or by patient choice who, however, are eligible for radical RT or CRT; ≥ 1 measurable lesion by RECIST v1.1. This is a Phase Ib/II, single-center, open-label, single-arm study, expected to expand to other center within the country. Durvalumab will be administered as neoadjuvant therapy before standard of care RT/CRT to 30 patients with untreated NSCLC not amenable for surgery but planned to undergo radical RT or CRT. The primary endpoint is the rate of patients without Dose-Limiting Toxicity (DLT). The study will be conducted in two parts; the first, DLT will be evaluated on a total of 18 patients over 3 cohorts; the second, an expansion cohort of 12 patients will be enrolled to further evaluate the safety, efficacy and feasibility of neoadjuvant durvalumab followed by standard of care RT/CRT. A single IV infusion of durvalumab 1500 mg will be administered at Visit 1. RT/RCT will be initiated between 4-5 weeks after. Standard RT/CRT and adjuvant treatment will be offered according to clinical practice. After completion of RT/RCT patients will be treated according to standard of care. A biomarker sub-study will be performed. Tumor and immune cells phenotype, somatic genetic alterations evaluation of tumor sample and ctDNA will be assessed. NCT05267392. IPO-Porto and AstraZeneca.