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CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFRm Non-Small-Cell Lung Cancer: A Brief Report

Open AccessPublished:January 11, 2023DOI:https://doi.org/10.1016/j.jtho.2022.12.021
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      ABSTRACT

      Background

      CD73 is overexpressed in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) and may promote immune evasion, suggesting potential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase Ib/II study (NCT03381274) evaluated the anti-CD73 antibody oleclumab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.

      Methods

      Patients had tissue T790M-negative NSCLC with TKI-sensitive EGFR mutations following progression on a first- or second-generation EGFR-TKI, and were osimertinib-naïve. 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 endpoints included safety and objective response rate (ORR) by RECIST v1.1.

      Results

      By July 9, 2021, 5 patients received DL1 and 21 received DL2. Respectively, 60.0% and 85.7% had any grade treatment-related adverse events (TRAEs) and 20.0% and 14.3% had grade 3 TRAEs. No dose-limiting toxicities, serious TRAEs, or deaths occurred. Four patients were T790M-positive on retrospective circulating tumor DNA (ctDNA) testing; 3 had objective partial responses. In patients who were T790M-negative in tumor and ctDNA, ORR 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.

      Conclusions

      Oleclumab plus osimertinib showed evidence of moderate activity with acceptable tolerability in previously treated patients with advanced EGFR-mutated NSCLC.

      Keywords