Bayer Launches Phase III Trial of HER2 Inhibitor BAY 2927088 Head-to-Head Against Keytruda in NSCLC

▎Armstrong

On June 11, 2024, Bayer registered a Phase III clinical trial on Clinicaltrials.gov for BAY 2927088 as a first-line treatment for HER2-activated mutant non-small cell lung cancer.

This Phase III clinical trial plans to enroll 278 patients with HER2-activating mutations and locally advanced non-small cell lung cancer, with an expected preliminary completion date of June 2026.

This Phase III clinical trial is a head-to-head comparison with the standard therapy of PD-1 + chemotherapy.

BAY 2927088 is a small molecule inhibitor of mEGFR/HER2.

EGFR mutation is the most common genetic mutation in non-small cell lung cancer, typically occurring in Exon19 and Exon21. However, various mutations in Exon20 are often insensitive to EGFR-TKIs. In 2021, the FDA successively approved the EGFR/cMET bispecific antibody and Takeda's TAK-788 for the treatment of non-small cell lung cancer patients with EGFR exon20 insertions.

At the 2023 ESMO CongressBayer announced the Phase 1/2 clinical data of BAY 2927088 for the treatment of EGFR/HER2-mutant NSCLC in later lines, with an overall ORR of 26%, and an ORR of 60% in patients with HER2 exon 20 insertion mutations (n = 20).On February 26, 2024, BAY2927088 received FDA Breakthrough Therapy Designation for the treatment of non-small cell lung cancer patients with HER2 activating mutations. Therefore, this Phase III clinical trial is limited to NSCLC patients with HER2 activating mutations.

Summary

HER2 activating mutations account for 2-4% of non-small cell lung cancer patients, and there is currently a lack of FDA fully approved treatment options. Outside of the highly competitive EGFR exon20ins space, Bayer has identified HER2 exon20ins as a breakthrough.