Boehringer and Bayer's Oral Drugs Show Promise in Early HER-2 Mutant Lung Cancer Trials

At the 2024 World Conference on Lung Cancer in San Diego, significant developments in the treatment of non-small cell lung cancer (NSCLC) with HER2 mutations were unveiled. Boehringer Ingelheim and Bayer presented promising data on their new oral drugs, zongertinib and BAY 2927088, which aim to compete with the currently approved antibody-drug conjugate, Enhertu, developed by AstraZeneca and Daiichi Sankyo.

HER2 mutations in NSCLC drive disease progression, but treatment options for this rare mutation are scarce. Enhertu is currently the only approved targeted therapy. The new drugs from Boehringer Ingelheim and Bayer are showing strong potential to provide alternative treatments.

Boehringer Ingelheim’s zongertinib and Bayer’s BAY 2927088 showed objective response rates of 66.7% and 72.1%, respectively, in phase 1b and phase 1/2 trials. Both drugs target HER2, a tyrosine kinase found in cell membranes, with Bayer’s drug also addressing mutations in epidermal growth factor receptors (EGFR). The trials included patients with HER2-mutated lung cancer.

In the Beamion LUNG-1 trial, zongertinib demonstrated tumor shrinkage in 94% of patients. Among those receiving the 120-mg dose, 17% experienced grade 3 or higher adverse events, while 19% of those on the 240-mg dose reported similar side effects, primarily mild ones like diarrhea and rash. Importantly, only 3% of patients discontinued treatment due to these side effects. The drug also controlled asymptomatic brain metastases in nearly three-fourths of patients on the 120 mg dose, a significant finding given that brain metastases occur in up to 30% of HER2-mutated NSCLC cases.

Bayer’s SOHO-1 trial saw one patient’s cancer completely disappear. The median duration of response was 8.7 months, and median progression-free survival was 7.5 months. Diarrhea was again the most common side effect, with three patients (6.8%) discontinuing treatment due to adverse effects.

Both drugs are moving into phase 3 trials, with Boehringer Ingelheim’s expected to conclude in May 2028 and Bayer’s by the end of 2026. While zongertinib and BAY 2927088 are small molecule inhibitors, contrasting with Enhertu’s antibody-drug conjugate mechanism, they potentially offer complementary treatment options. According to Dr. Xiuning Le, an oncologist at the University of Texas MD Anderson Cancer Center who leads the Bayer study, combining these small molecules with Enhertu could result in synergistic effects, enhancing tumor shrinkage and response duration.

As competition heats up, AstraZeneca and Daiichi Sankyo continue to expand Enhertu's application across various cancer types. Enhertu achieved $893 million in revenue in the second quarter of 2024, marking a 1.6% increase from the previous quarter.

These advancements represent a significant step forward in offering more diverse and potentially more effective treatment options for patients with HER2-mutated NSCLC, a challenging and rare subset of lung cancer.

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