2023 World Conference on Lung Cancer (Posters)-P1.12. Combining Anti-HER3 Antibody, HMBD-001, with EGFR Inhibition and Chemotherapy may Improve Treatment Outcomes in SqNSCLC

P1.12. Combining Anti-HER3 Antibody, HMBD-001, with EGFR Inhibition and Chemotherapy may Improve Treatment Outcomes in SqNSCLC - PDF(Abstract)

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A study presented at WCLC 2023 discusses the potential of combining an anti-HER3 antibody, HMBD-001, with EGFR inhibition and chemotherapy as a treatment strategy for squamous non-small cell lung cancer (sqNSCLC). SqNSCLC, which accounts for about 30% of lung cancers, has a poorer prognosis compared to other subtypes of NSCLC. The study highlights the genetic aberrations commonly found in sqNSCLC, including amplifications of chromosome 3q (Chr3q) and loss of chromosome 3p (Chr3p), as well as amplification of chromosome 7p (Chr7p) encoding EGFR. These genetic alterations lead to increased oncogenic signaling through the MAPK and PI3K pathways involving EGFR and HER3. Previous attempts to target HER3 have been limited in efficacy due to suboptimal HER3 inhibition and lack of biomarker stratification to select patients who would benefit from HER3 inhibition. However, the study suggests that combined inhibition of HER3 and EGFR may be more effective in blocking these signaling pathways. HMBD-001, a potent HER3-targeting antibody, is currently being evaluated in a Phase I/IIa trial in patients with HER3-expressing advanced solid tumors. In vitro and pre-clinical models of sqNSCLC demonstrate that HMBD-001 robustly inhibits tumor growth and that combining it with cetuximab and/or docetaxel shows potent tumor growth inhibition. These combinations are well tolerated and lead to sustained inhibition of tumor growth. The study concludes that genetic alterations in sqNSCLC activate the HER3 and EGFR pathways and that the combination of HMBD-001, EGFR inhibition, and chemotherapy has the potential to significantly improve clinical outcomes. Phase Ib clinical trials in biomarker-selected populations of sqNSCLC are planned for the second half of 2023.

Asset Subtitle

Dipti Thakkar

Meta Tag

Speaker Dipti Thakkar

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

WCLC 2023

anti-HER3 antibody

HMBD-001

EGFR inhibition

chemotherapy

squamous non-small cell lung cancer

sqNSCLC

genetic aberrations

MAPK pathway

PI3K pathway