2022 World Conference on Lung Cancer (ePosters)-EP08.02-049. A Phase I Trial of the HER2 Exon 20 Inhibitor, BI 1810631, In Patients With Advanced Solid Tumors With HER2 Aberrations

EP08.02-049. A Phase I Trial of the HER2 Exon 20 Inhibitor, BI 1810631, In Patients With Advanced Solid Tumors With HER2 Aberrations

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Researchers presented the results of a phase I clinical trial evaluating the efficacy of BI 1810631, a HER2-selective tyrosine kinase inhibitor (TKI), in patients with advanced solid tumors harboring HER2 aberrations. The study aimed to address the unmet need for targeted therapy against HER2 mutations in solid tumors, particularly in non-small cell lung cancer (NSCLC). HER2 mutations occur in 2-4% of NSCLC tumors, with ex20ins mutations being the most common.<br /><br />Historically, HER2 ex20ins mutations have shown poor response to TKIs, and TKIs that inhibit both EGFR and HER2 have been limited by toxicity. BI 1810631 is a novel TKI that selectively binds to the tyrosine kinase domain of HER2 receptors, inhibiting both wild-type and mutant HER2, including ex20ins. It avoids the toxicity associated with inhibiting wild-type EGFR and has the potential for better safety and efficacy compared to TKIs that bind to both HER2 and EGFR receptors.<br /><br />The phase I trial is divided into two parts: Phase Ia and Phase Ib. Phase Ia aims to determine the safety, tolerability, and pharmacokinetics (PK) of BI 1810631 as monotherapy in patients with advanced/metastatic solid tumors harboring HER2 aberrations. The maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) will also be determined. Phase Ib will further investigate the safety and efficacy of the RP2D in patients with NSCLC harboring HER2 TKD mutations.<br /><br />Preliminary results from the study showed that 13 patients have been treated as of June 2022. The trial is ongoing, and the futility analysis will be performed once 10 patients are evaluable for objective response. If two or more responses are observed, an additional 20 patients will be enrolled.<br /><br />This phase I trial provides hope for patients with HER2-mutant solid tumors, especially those with NSCLC. BI 1810631, a HER2-selective TKI, has the potential to offer a targeted therapy option with improved efficacy and tolerability. Further research is needed to determine the optimal dose and evaluate the long-term effectiveness of BI 1810631 in this patient population.

Asset Subtitle

Frans Opdam

Meta Tag

Speaker Frans Opdam

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

BI 1810631

HER2-selective tyrosine kinase inhibitor

phase I clinical trial

solid tumors

HER2 aberrations

non-small cell lung cancer

ex20ins mutations

EGFR

safety and efficacy

targeted therapy