Boehringer's Zongertinib Shows Promise in Treated HER2 Mutated Lung Cancer

Boehringer Ingelheim recently reported promising results from a Phase Ib analysis of the Beamion LUNG-1 trial, which evaluated the efficacy of zongertinib (BI 1810631) in patients with advanced non-small cell lung cancer (NSCLC) harboring activating HER2 mutations. The study, which targeted pre-treated patients, demonstrated a meaningful objective response rate (ORR) and an acceptable safety profile.

The findings from this trial were disclosed during the Presidential Symposium at the IASLC 2024 World Conference on Lung Cancer (WCLC). They indicated that zongertinib achieved an ORR of 66.7%, as assessed by blinded independent central review (BICR). Additionally, preliminary data showed an intracranial response rate of 33% and a disease control rate (DCR) of 74% in patients with brain metastases.

As of May 2024, the trial included 132 patients who received either 120 mg or 240 mg of zongertinib daily. The data revealed that tumor shrinkage occurred in 94% of patients across both dosage groups, based on investigator assessment, with the primary endpoint being met at the 120 mg dosage. This part of the trial also explored dose optimization, where zongertinib demonstrated a 72.4% response rate for the 120 mg group and 78.2% for the 240 mg group, alongside DCRs of 95% and 100%, respectively.

The trial also highlighted zongertinib's activity in treating brain metastases. For patients with asymptomatic brain metastases, the drug achieved a confirmed objective response rate of 33% for the 120 mg group and 40% for the 240 mg group, with DCRs of 74% and 92%, respectively. This is noteworthy as the central nervous system is a common site of metastasis in NSCLC, often leading to a poor prognosis and reduced quality of life.

Dr. John Heymach of The University of Texas MD Anderson Cancer Center, the principal investigator, emphasized the potential impact of these results. He noted that patients with activating HER2 mutations in NSCLC have limited treatment options and generally poor prognoses, with only about half responding to first-line treatments.

Zongertinib, an investigational oral HER2 tyrosine kinase inhibitor, shows promise in filling this treatment gap. Designed to avoid interactions with wild-type EGFR, the drug aims to reduce associated toxicities. A global Phase III trial, Beamion LUNG-2, is currently underway to further evaluate zongertinib against the standard of care in first-line treatment settings.

Paola Casarosa, a member of Boehringer Ingelheim's Board of Managing Directors, highlighted the drug's potential role in future lung cancer treatments, emphasizing its efficacy and tolerability. She reiterated the company's commitment to advancing novel therapies for cancer patients.

The safety profile of zongertinib was consistent across the 120 mg and 240 mg doses. Most treatment-related adverse events (TRAEs) were mild and manageable, with a low discontinuation rate of 3% due to toxicity. No new safety concerns or treatment-related interstitial lung diseases were observed. The trial reported Grade 3 or higher TRAEs in 17% of the 120 mg group and 19% of the 240 mg group, with the most common being mild diarrhea and rash.

With two-thirds of the patients still undergoing treatment at the data cut-off, more comprehensive data on progression-free survival (PFS) and duration of response (DoR) are expected later this year.

Lung cancer, particularly NSCLC, remains a significant health challenge, often diagnosed at advanced stages with limited survival rates. Up to 4% of lung cancers are driven by HER2 mutations, which promote uncontrolled cell growth and tumor spread. Thus, the development of targeted treatments like zongertinib is crucial.

Zongertinib, granted FDA Fast Track Designation in 2023 and Breakthrough Therapy Designation in 2024, is being closely monitored for its potential to become a key therapy for NSCLC with HER2 mutations. The Phase Ib results from the Beamion LUNG-1 trial underscore its potential effectiveness and manageable safety profile, offering hope for improved outcomes in this patient population.

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