Some patients with non-small cell lung cancer (NSCLC) have mutations in a gene called human epidermal growth factor receptor 2 (HER2), which drives their disease progression. Treatment options are limited for patients with this rare mutation, with only AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu approved to target it.
At the 2024 World Conference on Lung Cancer in San Diego, two rivals shared data on new oral drugs looking to challenge Enhertu’s dominance. Boehringer Ingelheim’s zongertinib and Bayer’s BAY 2927088 elicited objective response rates of 66.7% and 72.1% in their respective phase 1b and phase 1/2 trials, the companies said Monday.
Both drugs target HER2, which is a tyrosine kinase embedded in the membranes of cells, while Bayer’s drug also targets mutations in epidermal growth factor receptors. Both trials enrolled patients with HER2-mutated lung cancer.
In the Beamion LUNG-1 trial, BI's zongertinib shrank tumors in 94% of all patients. In the study, 17% of patients who received the 120-mg dose and 19% who received the 240-mg dose experienced adverse events of grade 3 or higher, with the most common side effects being mild, such as diarrhea and rash.
Boehringer will present progression-free survival and duration of response data later this year, according to the release. In Beamion LUNG-1, 3% of patients had to discontinue treatment with zongertinib due to the side effects, the release said.
Zongertinib also controlled the asymptomatic brain cancer of patients whose cancer had metastasized, with almost three-fourths of these patients given 120 mg showing disease control, as determined by tumor response and progression, according to BI. Brain metastases occur in up to 30% of patients with HER2-mutated NSCLC, according to the press release.
In the SOHO-1 trial, one patient given BAY 2927088 had their cancer completely disappear. The median duration of response in the study was 8.7 months, and median progression-free survival came in at 7.5 months. Diarrhea was again the most common side effect; three patients (6.8%) had side effects that led to them stopping treatment.
Both drugs are now in phase 3 trials, with both set to wrap up in May 2028.
While Enhertu is an antibody-drug conjugate, both zongertinib and BAY 2927088 are small molecules with a different mechanism of action, meaning they could potentially be used in combination with Enhertu.
"One can imagine that the ADC drug binds to the membrane, and then the TKI goes into the ATP-binding pocket [of the protein]," Xiuning Le, M.D., Ph.D., an oncologist at the University of Texas MD Anderson Cancer Center and leader of the Bayer study, said in a press conference. "And they have a truly synergistic, on-target, deep inhibition so that tumor shrinkage and duration can be fantastic."
A combination like that still needs to be tested preclinically and clinically, she added.
As the dueling pharmas gear up to potentially take on Enhertu, AstraZeneca and Daiichi Sankyo have been working to expand their drug’s dominance across different cancer types. Enhertu brought in $893 million in the second quarter of 2024, a 1.6% increase from the first quarter.