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HERTHENA-Lung02: phase III study of patritumab deruxtecan in advanced EGFR-mutated NSCLC after a third-generation
Tony Mok1, Pasi A Jänne2, Makoto Nishio3
1Department of Clinical Oncology, State Key Laboratory of Translational Oncology & Chinese University of Hong Kong, Hong Kong, Hong Kong PRC.
Abstract:
After disease progression on EGFR tyrosine kinase inhibitor (TKI) therapy, patients with EGFR-mutated NSCLC who are then treated with platinum-based chemotherapy (PBC) obtain only limited clinical benefit with transient responses. Therapies with greater efficacy and tolerable safety profiles are needed in this setting. The receptor tyrosine kinase HER3 is widely expressed in NSCLC, and increased expression is associated with poor treatment outcomes. In the U31402-A-U102 phase I trial, HER3-DXd showed promising antitumor activity with manageable safety in heavily pre-treated patients with EGFR-mutated NSCLC across a range of tumor HER3 expression levels and EGFR TKI resistance mechanisms. HERTHENA-Lung02 is the first phase III trial to evaluate the safety and efficacy of HER3-DXd versus PBC in patients with progression on a third-generation EGFR TKI. Clinical Trial Registration: NCT05338970 (clinicaltrials.gov); 2021-005879-40 (EudraCT Number).
Insights
New HER3-DXd antibody-drug conjugate shows promise for non-small cell lung cancer (NSCLC) patients who progressed on EGFR tyrosine kinase inhibitor (TKI) therapy. This investigational therapy offers a potential new option beyond platinum-based chemotherapy (PBC) for advanced NSCLC.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) with EGFR mutations often progresses after tyrosine kinase inhibitor (TKI) therapy.
- Platinum-based chemotherapy (PBC) offers limited benefit in this refractory setting.
- HER3 receptor tyrosine kinase is implicated in NSCLC progression and poor outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of HER3-DXd compared to PBC in patients with EGFR-mutated NSCLC post-third-generation EGFR TKI progression.
- To assess HER3-DXd's antitumor activity in a heavily pre-treated NSCLC population.
Main Methods:
- HERTHENA-Lung02 is a Phase III randomized controlled trial.
- Patients with EGFR-mutated NSCLC and disease progression on a third-generation EGFR TKI are randomized to HER3-DXd or PBC.
- Tumor HER3 expression levels and resistance mechanisms are evaluated.
Main Results:
- Phase I data (U31402-A-U102) indicated promising antitumor activity and manageable safety for HER3-DXd in heavily pre-treated NSCLC patients.
- HER3-DXd demonstrated efficacy across varying HER3 expression levels and EGFR TKI resistance mechanisms.
Conclusions:
- HER3-DXd represents a potential novel therapeutic strategy for EGFR-mutated NSCLC patients progressing on EGFR TKIs.
- HERTHENA-Lung02 trial will provide crucial data on HER3-DXd's role in this challenging clinical scenario.
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