Zongertinib Demonstrates High Objective Response Rate in Previously Treated Advanced Non-Small Cell Lung Cancer

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Boehringer Ingelheim’s zongertinib showed promise in previously treated patients with advanced non-small cell lung cancer (NSCLC) with activating HER2 mutations, according to results from the Phase Ib Beamion LUNG-trial. According to the company, the treatment demonstrated a statistically significant objective response rate (ORR) and was generally well tolerated.¹

"These new data could represent positive news in the future treatment of non-small cell lung cancer patients with activating HER2 mutations," said the trial’s principal investigator, John Heymach, MD, PhD, The University of Texas MD Anderson Cancer Center, in a press release. "While these mutations are rare, they are critical drivers in a subset of non-small cell lung cancer cases, and current treatment options are severely limited. Patients with this type of cancer typically face a poor prognosis, with approximately 50% responding to first-line treatment and only 20% responding to second-line therapy.”

The open-label, dose escalation Beamion LUNG-1 trial included a dose confirmation and expansion portion to evaluate zongertinib monotherapy in patients with advanced or metastatic solid tumors and NSCLC with activating HER2 mutations. The first part of the study was open to adults with multiple forms of cancer that were not treated successfully with prior therapies. The second part was open to patients with NSCLC with a specific mutation in the HER2 gene. At the time of assessment, 132 patients were treated with 120 mg/240 mg of zongertinib once a day.

Results found that zongertinib lead to an ORR rate of 66.7%, which effectively achieved the primary endpoint of the study. Additionally, tumor shrinkage of any size was reported in 94% of all patients across doses, per investigator assessment. Data on progression-free survival and duration of response are expected to be reported later in the year.

Zongertinib was generally well tolerated at the 120 mg and 240 mg doses, with no deaths reported during treatment. Three percent of patients discontinued treatment due to adverse events (AEs), while only 11% of patients experienced AEs that lead to a dose reduction. No new safety signals were observed in the study, and grade 3 or higher treatment-related AEs occurred in 17% (120 mg) and 19% (240 mg) of patients treated with zongertinib. Common AEs included rash and diarrhea.¹

According to Yale Medicine, both NSCLC and small cell lung cancer (SCLC) account for 230,000 newly diagnosed cases of lung cancer in the United States on a yearly basis. While NSCLC progresses much slower than SCLC, 40% of NSCLCs will have spread beyond the lungs by the time it is diagnosed. Up to 85% of all lung cancers are NSCLC, making it the most common form of lung cancer. Types of NSCLC include adenocarcinoma, which makes up 40% of all NSCLC diagnoses, squamous cell carcinoma, making up 25% to 30%, and large cell carcinoma, making up anywhere from 10% to 15%.²

“Zongertinib’s efficacy and tolerability profile has the potential to become part of the future treatment landscape for patients with HER2 mutated lung tumors. Zongertinib is a perfect example of our approach to science in the discovery and development of novel treatments. Boehringer is committed to providing breakthrough therapies for cancer patients, and we look forward to advancing the zongertinib clinical program,” said Paola Casarosa, board of managing directors, head, innovation unit, Boehringer Ingelheim, in the press release.

References

1. Boehringer’s zongertinib shows encouraging efficacy and tolerability profile in previously treated HER2 mutated lung cancer patients. Boehringer Ingelheim. September 9, 2024. Accessed September 10, 2024. https://www.boehringer-ingelheim.com/human-health/cancer/lung-cancer/zongertinib-positive-results-non-small-cell-lung-cancer

2. Non-Small Cell Lung Cancer. Yale Medicine. Accessed September 10, 2024. https://www.yalemedicine.org/conditions/non-small-cell-lung-cancer