Zongertinib

PALO ALTO, Calif.--( BUSINESS WIRE )--Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, today announced a collaboration with Boehringer Ingelheim to pursue the regulatory approval and commercialization of the Guardant360 ® CDx liquid biopsy as a companion diagnostic (CDx) for zongertinib, an investigational covalent tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). As part of the collaboration, the Guardant360 CDx blood test will provide comprehensive genomic profiling (CGP) of tumors to identify actionable biomarkers that allow targeted therapy selection and help identify NSCLC patients with HER2 mutations who may be eligible for treatment with Boehringer’s investigational zongertinib after it is approved by health authorities. “Many of the 40,000 people diagnosed worldwide every year with NSCLC with a HER2 mutation may respond poorly to standard chemotherapy and immunotherapy,” said Helmy Eltoukhy, Guardant Health chairman and co-CEO. “This collaboration with Boehringer Ingelheim to pursue approval of the Guardant360 CDx test as a companion diagnostic would allow oncologists, using a simple blood draw, to identify patients with advanced lung cancer who have HER2 mutations targeted by zongertinib and could benefit from this investigational therapy.” The first FDA-approved comprehensive liquid biopsy for all advanced solid tumors, Guardant360 CDx is approved as a companion diagnostic for multiple targeted therapies in NSCLC. It is also the only FDA-approved CDx to identify patients eligible for breast cancer therapy targeting ESR1 mutations and has broad commercial and Medicare coverage. About Guardant Health Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care and accelerating new cancer therapies by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and treatment selection for patients with advanced cancer. For more information, visit guardanthealth.com and follow the company on LinkedIn , X (Twitter) and Facebook . Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential utilities, values, benefits and advantages of Guardant Health’s liquid biopsy tests or assays, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health’s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2023, and any current and periodic reports filed with or furnished to the Securities and Exchange Commission thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health’s views as of any date subsequent to the date of this press release.

Both drugs are now in phase 3 trials, with Boehringer Ingelheim’s set to wrap up in May 2028 and Bayer’s expected to finish by the end of 2026. 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.