oleclumab + osimertinib

Oleclumab + osimertinib is a combination therapy under investigation for advanced non–small-cell lung cancer (NSCLC) with EGFR mutations that are T790M-negative and have progressed after first- or second-generation EGFR tyrosine kinase inhibitors. Oleclumab is a monoclonal antibody targeting CD73, an ectoenzyme overexpressed in EGFR-mutated NSCLC that promotes immune evasion by generating immunosuppressive adenosine. By inhibiting CD73, oleclumab aims to enhance anti-tumor immunity. Osimertinib is a third-generation small molecule EGFR tyrosine kinase inhibitor that selectively targets both sensitizing and T790M resistance mutations in the epidermal growth factor receptor. The combination seeks to overcome resistance mechanisms and improve outcomes compared to monotherapy. Clinical studies have shown moderate activity and acceptable tolerability for this regimen in previously treated patients[1][2][4].