BDTX-1535 – A MasterKey EGFR Inhibitor Targeting Classical, Non-Classical, and the C797S Resistance Mutation To Address The Evolved Landscape Of EGFR Mutant NSCLC

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Christine Lovly, MD, PhD, shares data on BDTX-1535, a “masterkey” EGFR inhibitor targeting classical, non-classical, and the C797S resistance mutation in patients with EGFR mutant non-small cell lung cancer (NSCLC), from a presentation at AACR 2024.

BDTX-1535 – A MasterKey EGFR Inhibitor Targeting Classical, Non-Classical, and the C797S Resistance Mutation to Address the Evolved Landscape of EGFR Mutant NSCLC

Dr Lovly on the Investigation of BDTX-1535 in NSCLC

Christine M. Lovly, MD, PhD, Ingram Associate Professor of Cancer Research, associate professor, medicine (hematology/oncology), Vanderbilt-Ingram Cancer Center, discusses the investigation of the EGFR inhibitor BDTX-1535 in patients with non–small cell lung cancer (NSCLC).

 mutations in lung cancer were discovered approximately 20 years ago, the need for improved targeted therapies for patients with 

-mutant NSCLC remains high, and new drugs should be developed to address this need, Lovly says. One novel agent, BDTX-1535, is a fourth-generation EGFR inhibitor that is currently under investigation in clinical trials. This agent may have broad activity across several types of 

 mutations, including classical, nonclassical, and concurrent classical and nonclassical alterations, Lovly explains. BDTX-1535, a so-called pan-EGFR TKI, may also be active against resistance mutations, such as 

C797S mutations, that emerge with the use of osimertinib (Tagrisso), Lovly notes.

Preclinical data have shown the efficacy of BDTX-1535 in the therapeutic window between targeting 

, Lovly emphasizes. Furthermore, emerging clinical data from a phase 1/2 trial (NCT05256290) have demonstrated preliminary efficacy with the agent against classical 

 C797S mutations. For instance, pharmacokinetic data from the phase 1 trial showed that the agent targeted the 

mutation spectrum at a well-tolerated oral dose of 100 mg to 200 mg daily. Additionally, the phase 1 trial showed that BDTX-1535 drove clearance of classical 

 mutations in 7 out of 7 evaluable patients, nonclassical 

 mutations in 4 out of 4 evaluable patients, 

 C797S resistance mutations in 6 out of 6 evaluable patients, and plasma circulating tumor DNA in 9 out of 9 evaluable patients.

Although research with BDTX-1535 is still at an early stage, further findings with this agent are anticipated. Lovly says. This agent may help personalize the 

-mutant NSCLC treatment paradigm, Lovly concludes.

Christine M. Lovly, MD, PhD, discusses the investigation of the EGFR inhibitor BDTX-1535 in patients with non–small cell lung cancer.

Christine M. Lovly, MD, PhD

Articles

BDTX-1535 – A MasterKey EGFR Inhibitor Targeting Classical, Non-Classical, and the C797S Resistance Mutation to Address the Evolved Landscape of EGFR Mutant NSCLC

Dr Lovly on the Investigation of BDTX-1535 in NSCLC