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 <em>HER2</em>-mutated or overexpressed/amplified solid tumors.

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.

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.

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Author Details

Alison Schram

Memorial Sloan Kettering Cancer Center, New York, NY

Abstract Details

Meeting

2025 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Abstract Disclosure

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 HER2-mutated or overexpressed/amplified solid tumors.

Author Details

Alison Schram

Abstract Details

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