Beamion PANTUMOR-1: A phase II, multicenter, multicohort, open-label trial to evaluate the efficacy and safety of the oral HER2-selective tyrosine kinase inhibitor zongertinib for the treatment of <i>HER2</i> -mutated or overexpressed/amplified solid

TPS3187 Background: While it is well known that HER2 overexpression, amplification, and mutation drives various tumors, there remains an unmet need for effective, oral, HER2-targeted therapies. Zongertinib is an irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing EGFR, thereby limiting associated toxicities. In the ongoing Phase Ia/Ib trial (NCT04886804), zongertinib showed manageable safety and confirmed responses in patients (pts) with HER2-overexpressed/amplified and HER2 -mutant tumors (Wilding et al, Cancer Discov. 2024). Based on these encouraging data, the Beamion PANTUMOR-1 basket trial (NCT06581432) is evaluating the efficacy and safety of zongertinib monotherapy in pts with HER2 -mutant or HER2-overexpressed/amplified solid tumors. Methods: In this global Phase II basket trial, ~200 pts with HER2-driven ( HER2 -mutant or HER2-overexpressed/amplified) tumors will be enrolled at ~60 sites in 13 countries. Pts will be enrolled to 10 cohorts: 8 cohorts of specific tumor types and 2 tumor-agnostic cohorts (see Table). The specific tumor type cohorts will initially recruit 10 pts, with potential for expansion to up to 20 pts after an interim analysis. In the tumor-agnostic cohorts, 20 pts will be recruited directly without an interim analysis. Pts will receive 120 mg zongertinib until disease progression, unacceptable toxicity, or withdrawal. Patients must be ≥18 years old, have documented HER2-positive (HER2-overexpressed/amplified) status or a HER2 mutation (established by local testing), ≥1 measurable lesion outside the central nervous system, an ECOG performance score of 0 or 1, and have progressed following prior treatment or have no alternative treatment options. Exclusion criteria include HER2 -mutant non-small cell lung cancer (NSCLC) and previous/concomitant malignancies. Primary endpoint is objective response, as assessed by central independent review according to 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. Enrollment is ongoing. Clinical trial information: NCT06581432 . HER2 overexpression/amplification cohorts Tumor type HER2 mutation cohorts Tumor type Cohort 1 Urothelial cancer Cohort 7 Urothelial cancer Cohort 2 Biliary tract cancer Cohort 8 Breast cancer Cohort 3 Uterine cancer Cohort 9 Gastroesophageal cancer Cohort 4 Cervical cancer Cohort 10 Other HER2 -mutant solid tumors † Cohort 5 Non-squamous NSCLC Cohort 6 Other HER2 overexpressed/amplified solid tumors* *Except breast cancer, gastric, gastroesophageal junction, or esophageal adenocarcinoma. † Except NSCLC.