Human epidermal growth factor receptor 2 (HER2, encoded by ERBB2) alterations are known oncogenic drivers in many solid tumors. Zongertinib is a novel, oral, irreversible, HER2-selective tyrosine kinase inhibitor that spares wild-type epidermal growth factor receptor, thereby limiting associated toxicities. In a Phase Ia/Ib trial (NCT04886804), zongertinib demonstrated encouraging activity with a manageable safety profile in HER2-altered tumors (HER2 overexpression, amplification, or mutations).The Phase II, open-label, Beamion PANTUMOR-1 basket trial (NCT06581432) is evaluating the efficacy and safety of zongertinib monotherapy in previously treated patients with HER2-positive (HER2-overexpressed/amplified) or HER2-mutant solid tumors. Patients with HER2-positive tumors will be enrolled to one of eight cohorts: urothelial, biliary tract, uterine, cervical, non-squamous lung, salivary gland, colorectal or tumor agnostic. Patients with HER2-mutant tumors will be enrolled to one of five cohorts: urothelial, breast, gastroesophageal, biliary tract or tumor agnostic. Patients will receive zongertinib 120 mg orally once daily until disease progression (RECIST v1.1), unacceptable toxicity, death, or withdrawal of patient consent, whichever occurs first. The primary endpoint is objective response (central independent review, RECIST v1.1). Secondary endpoints include duration of response, progression-free survival, disease control, occurrence of treatment-emergent adverse events, and health-related quality of life. Recruitment is ongoing in 13 countries globally.Clinical trial registration http://www.clinicaltrials.gov identifier is NCT06581432.
Keywords: Beamion PANTUMOR-1; HER2; Zongertinib; basket trial; solid tumors.
Many cells in the body produce a protein called human epidermal growth factor receptor 2 (HER2), which plays a crucial role in determining when healthy cells should grow and divide. If cells make too much HER2, or if the HER2 gene carries a mutation, it can cause cancer. A subset of many types of cancer, such as breast, lung, urothelial, biliary tract, cervical, uterine, salivary gland and gastroesophageal cancers, are known to be associated with changes (alterations) in HER2. Over the past 20 years, a lot of progress has been made with medications that target HER2; however, certain medications may not be available for specific HER2 alterations or tumor types, and side effects and administration challenges potentially limit their use. Zongertinib is a new drug taken as a tablet that specifically targets HER2. In a clinical study (NCT04886804), zongertinib effectively caused tumors to shrink in most patients with HER2-mutant lung cancer, with diarrhea and rash being the most common side effects; these were both manageable. Based on encouraging results from other early clinical studies, an additional zongertinib study has been designed called Beamion PANTUMOR-1. This study is being undertaken in previously treated patients with a range of different cancers with HER2 alterations. In this study, patients will receive zongertinib orally once daily. The main objectives are to assess whether zongertinib can shrink tumors, help identify potential treatment side effects, and determine the impact on patients’ quality of life.