CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFR-Mutated NSCLC: A Brief Report

Introduction: CD73 is overexpressed in EGFR-mutated NSCLC and may promote immune evasion, suggesting po-tential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase 1b-2 study (NCT03381274) evaluated the anti-CD73 antibody oleclu-mab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.Methods: Patients had tissue T790M-negative NSCLC with TKI-sensitive EGFR mutations after progression on a first -or second-generation EGFR TKI and were osimertinib naive. They received osimertinib 80 mg orally once daily plus oleclumab 1500 mg (dose level 1 [DL1]) or 3000 mg (DL2) intravenously every 2 weeks. Primary end points included safety and objective response rate by Response Evaluation Criteria in Solid Tumors version 1.1.Results: By July 9, 2021, five patients received DL1 and 21 received DL2. Of these patients, 60.0% and 85.7% had any -grade treatment-related adverse events (TRAEs) and 20.0% and 14.3% had grade 3 TRAEs, respectively. No dose -limiting toxicities, serious TRAEs, or deaths occurred. Four patients were T790M positive on retrospective circulating tumor DNA (ctDNA) testing; three had objective partial re-sponses. In patients who were T790M negative in tumor and ctDNA, objective response rate was 25.0% at DL1 and 11.8% at DL2 (all partial responses); response durations at DL2 were 14.8 and 16.6 months. In patients receiving DL2, excluding those who were T790M positive by ctDNA, me-dian progression-free survival was 7.4 months, and median overall survival was 24.8 months. DL2 was the recom-mended phase 2 dose.Conclusions: Oleclumab plus osimertinib was found to have moderate activity with acceptable tolerability in pre-viously treated patients with advanced EGFR-mutated NSCLC.(c) 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Automated summary

This study evaluated the combination of the anti-CD73 antibody oleclumab with the third-generation EGFR TKI osimertinib in previously treated patients with advanced EGFR-mutated NSCLC. The treatment showed moderate activity and acceptable tolerability in this patient population.