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

• Published in: Journal of thoracic oncology Vol. 18; no. 5; p. 650
• Main Authors: Kim, Dong-Wan, Kim, Sang-We, Camidge, D Ross, Shu, Catherine A, Marrone, Kristen A, Le, Xiuning, Blakely, Collin M, Park, Keunchil, Chang, Gee-Chen, Patel, Sandip Pravin, Kar, Gozde, Cooper, Zachary A, Samadani, Ramin, Pluta, Michael, Kumar, Rakesh, Ramalingam, Suresh
• Format: Journal Article
• Language: English
• Published: United States 01-05-2023
• Subjects: 5'-Nucleotidase - antagonists & inhibitors; Aniline Compounds; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; ErbB Receptors; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mutation; Protein Kinase Inhibitors - pharmacology; Retrospective Studies; Non–small-cell lung cancer; CD73; EGFR TKI resistance; T790M-negative
• ISSN: 1556-1380
• DOI: 10.1016/j.jtho.2022.12.021

CD73 is overexpressed in EGFR-mutated NSCLC and may promote immune evasion, suggesting potential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase 1b-2 study (NCT03381274) evaluated the anti-CD73 antibody oleclumab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.
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.
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 responses. 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, median progression-free survival was 7.4 months, and median overall survival was 24.8 months. DL2 was the recommended phase 2 dose.
Oleclumab plus osimertinib was found to have moderate activity with acceptable tolerability in previously treated patients with advanced EGFR-mutated NSCLC.