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).

Although EGFR mutations in lung cancer were discovered approximately 20 years ago, the need for improved targeted therapies for patients with EGFR-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 EGFR 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 EGFRC797S 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 EGFR mutations and wild-type EGFR, Lovly emphasizes. Furthermore, emerging clinical data from a phase 1/2 trial (NCT05256290) have demonstrated preliminary efficacy with the agent against classical EGFR mutations, nonclassical EGFR mutations, and EGFR resistance mutations, including EGFR C797S mutations. For instance, pharmacokinetic data from the phase 1 trial showed that the agent targeted the EGFRmutation 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 EGFR mutations in 7 out of 7 evaluable patients, nonclassical EGFR mutations in 4 out of 4 evaluable patients, EGFR 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 EGFR-mutant NSCLC treatment paradigm, Lovly concludes.