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(Slides)

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A study conducted by Hummingbird Bioscience, in collaboration with Caris Life Sciences, suggests that combining the anti-HER3 antibody HMBD-001 with EGFR inhibition and chemotherapy could improve treatment outcomes for patients with squamous non-small cell lung cancer (sqNSCLC). SqNSCLC is a subtype of NSCLC with a poor prognosis and limited treatment options. The study found that genes on chromosome 3q involved in HER signaling are frequently amplified in sqNSCLC and have higher expression levels compared to non-squamous NSCLC. These amplifications lead to increased transcriptional activity of TP63, SOX2, and PIK3CA, which are involved in promoting HER3 and EGFR expression and enhancing activation of the PI3K pathway. In addition, EGFR on chromosome 7p is frequently amplified and upregulated in sqNSCLC, while TUSC2, a negative regulator of EGFR signaling, on chromosome 3p is deleted and downregulated. The study also demonstrated that sqNSCLC cell lines are more dependent on HER3 than EGFR.<br /><br />Inhibition of EGFR often leads to compensatory increases in HER3 activity and resistance to EGFR monotherapy. However, inhibiting HER3 signaling, either alone or in combination with EGFR inhibition and docetaxel (a second-line cytotoxic therapy), showed potential for improving clinical outcomes in sqNSCLC. HMBD-001, an anti-HER3 antibody, was found to potently inhibit PI3K signaling and showed anti-tumor activity in sqNSCLC as a monotherapy. When combined with cetuximab (an EGFR inhibitor) and docetaxel, HMBD-001 further enhanced the anti-tumor effect in sqNSCLC models.<br /><br />Based on these findings, Hummingbird Bioscience has initiated Phase Ib trials to investigate the potential of HMBD-001 in the treatment of sqNSCLC. The trials are being conducted in biomarker-selected populations of sqNSCLC. The study provides a unified hypothesis of the etiology and tumorigenesis in squamous cell carcinoma and highlights the role of anti-HER3 therapeutics.

Asset Subtitle

Dipti Thakkar

Meta Tag

Speaker Dipti Thakkar

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

Hummingbird Bioscience

Caris Life Sciences

anti-HER3 antibody

EGFR inhibition

chemotherapy

squamous non-small cell lung cancer

NSCLC

genes on chromosome 3q

HER signaling

sqNSCLC cell lines