Beamion LUNG-3: Adjuvant Zongertinib vs Standard Treatment in People With Completely Resected Stage II-IIIB NSCLC Harboring Activating HER2 TKD Mutations

Official title

Beamion LUNG-3: A Randomized, Controlled, Multi-center Trial Evaluating Zongertinib as an Adjuvant Monotherapy Compared With Standard of Care in Patients With Early-stage, Resectable Non-small Cell Lung Cancer (Stage II-IIIB) Harboring Tyrosine Kinase Domain Activating HER2 Mutations

Overview

Beamion LUNG-3 study evaluates whether zongertinib, an oral HER2-targeted treatment, can improve outcomes compared with standard adjuvant treatment in adults with completely resected Stage II-IIIB non-small cell lung cancer (NSCLC) whose tumors have activating HER2 tyrosine kinase domain (TKD) mutations. Eligible participants must have undergone curative-intent surgery and received guideline-appropriate perioperative systemic therapy, either neoadjuvant platinum-based chemotherapy with or without immunotherapy, or adjuvant platinum-based chemotherapy. Participants are randomized 1:1 to receive zongertinib or standard of care, which may consist of approved adjuvant immunotherapy or active surveillance, based on local practice guidelines. The main purpose of the study is to determine whether zongertinib can prolong disease-free survival compared to standard treatment. Safety and patient-reported outcomes are also assessed.

Detailed description

This is a global, randomized, open-label, Phase 3 study designed to assess the efficacy and safety of zongertinib as adjuvant therapy in participants with completely resected Stage II-IIIB NSCLC and HER2 TKD-activating mutations.

Participants must have undergone complete resection and received perioperative systemic therapy consistent with current standards, including either neoadjuvant platinum-based chemotherapy with or without immunotherapy, or adjuvant platinum-based chemotherapy.

After completing surgery and required systemic treatment, eligible participants are randomized 1:1 to receive either Zongertinib taken orally once daily for up to 3 years, or standard treatment, which may include an approved adjuvant immunotherapy agent administered according to its label, or observation, depending on local clinical practice and patient status.

The primary objective is to evaluate whether zongertinib improves disease-free survival (DFS) compared with standard treatment. Secondary objectives include overall survival (OS), safety, tolerability, and patient-reported outcomes.

Interventions

• Drug Zongertinib
  Zongertinib
• Drug Pembrolizumab
  Pembrolizumab
• Drug Atezolizumab
  Atezolizumab
• Drug Durvalumab
  Durvalumab
• Drug Nivolumab
  Nivolumab

Primary outcome measures

• Disease-free survival (DFS) by investigator's assessment [Time frame: up to 8 years and 5 months]

Secondary outcome measures (2)

• Key secondary endpoint: Overall survival (OS), defined as the time from randomization until death from any cause [Time frame: up to 8 years and 5 months]
• Occurrence of trial-related Adverse Events (AEs) ≥ Grade 3 from first treatment administration (or from randomization for patients in the observation arm) until the earliest of tumor recurrence or 3 years since treatment start [Time frame: up to 3 years]

Eligibility criteria

Inclusion criteria

• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
• Patients must be ≥18 years old or over the legal age of consent in their country
• Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use dual highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information and in the study protocol
• HER2 mutation: Documented Tyrosine kinase domain (TKD) activating Human epidermal growth factor receptor 2 (HER2) mutations
• Histology and tumor sample: Histologically confirmed diagnosis of primary NSCLC
• An archival tumor tissue sample must be submitted to the central laboratory after inclusion of the patient to retrospectively confirm the HER2 status
• Staging: Pretherapeutic classification not exceeding Stage IIIB
• Performance status and organ function:

• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Adequate organ function based on laboratory values Further inclusion criteria apply.

Exclusion criteria

• Diagnosis of NSCLC with mixed histology/positive neuroendocrine markers (synaptophysin/CD56)
• Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization
• Treatment with radiation therapy for primary NSCLC
• Co-occurring actionable mutation with approved targeted therapy (e.g. Epidermal growth factor receptor (EGFR) or Anaplastic lymphoma kinase (ALK))
• Any investigational drug within 5 half-lives of the compound or any of its related material, if known
• History or presence of

• Active or known pre-existing or history of non-infectious interstitial lung disease/pneumonitis
• Active infectious disease requiring systemic therapy
• Uncontrolled gastrointestinal disorders affecting drug intake/absorption
• Previous or concomitant malignancies within the last 3 years, except certain effectively treated cancers
• Significant and/or uncontrolled cardiovascular abnormalities, QT interval corrected for heart rate by Fridericia formula (QTcF) >470 msec, or ejection fraction <50% Further exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 28 centers

• ClinRé 001-022 (Premier Cancer Care and Infusion Center) — Fresno
• OPN Healthcare, Inc. — Glendale
• University of California Irvine — Irvine
• Sutter Health — Roseville
• University of California San Francisco — San Francisco
• Sarcoma Oncology Center — Santa Monica
• University of California Los Angeles — Santa Monica
• Northern California Kaiser Permanente — Vallejo
• … and 20 more centers

China · 28 centers

• China-Japan Friendship Hospital — Beijing
• Beijing Chest Hospital, Capital Medical University — Beijing
• The First Hospital of Jilin University — Changchun
• Xiangya Hospital, Central South University — Changsha
• Hunan Province Tumor Hospital — Changsha
• Sichuan Cancer Hospital — Chengdu
• West China Hospital, Sichuan University — Chengdu
• The First Affiliated Hospital,Sun Yat-sen University — Guangzhou
• … and 20 more centers

Japan · 25 centers

Center list to be confirmed — check the primary protocol.

Spain · 15 centers

Center list to be confirmed — check the primary protocol.

Germany · 9 centers

Center list to be confirmed — check the primary protocol.

France · 8 centers

Center list to be confirmed — check the primary protocol.

Italy · 8 centers

Center list to be confirmed — check the primary protocol.

South Korea · 8 centers

Center list to be confirmed — check the primary protocol.

Brazil · 7 centers

• Hospital de Amor — Barretos
• NewData Clinical Research - Maceió — Maceió
• Centro de Pesquisa Oncology Natal — Natal
• Centro Gaúcho Integrado de Oncologia, Hematologia, Ensino e Pesquisa — Porto Alegre
• CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia — Santo André
• ICESP - Instituto do Cancer do Estado de Sao Paulo — São Paulo
• A.C. Camargo — São Paulo

Taiwan · 6 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 6 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• Centro de Investigaciones Médicas y Desarrollo LC S.R.L. (LC Investigación) — CABA
• Hospital Britanico de Buenos Aires — CABA
• Centro Oncologico Korben — CABA
• Clinica Adventista Belgrano — CABA
• Instituto Medico Especializado Alexander Fleming — Capital Federal

Australia · 5 centers

• Royal North Shore Hospital — Sydney
• Princess Alexandra Hospital — Woolloongabba
• Flinders Medical Centre — Bedford Park
• Austin Health — Heidelberg
• St John of God Subiaco Hospital — Subiaco

Israel · 5 centers

Center list to be confirmed — check the primary protocol.

Mexico · 5 centers

Center list to be confirmed — check the primary protocol.

Hong Kong · 4 centers

Center list to be confirmed — check the primary protocol.

Portugal · 4 centers

Center list to be confirmed — check the primary protocol.

Romania · 4 centers

Center list to be confirmed — check the primary protocol.

Belgium · 3 centers

• Edegem - UNIV UZ Antwerpen — Edegem
• UZ Leuven — Leuven
• Centre Hospitalier Universitaire de Liège — Liège

Greece · 3 centers

Center list to be confirmed — check the primary protocol.

Austria · 2 centers

• Medical University of Innsbruck — Innsbruck
• Clinic Floridsdorf — Vienna

Canada · 2 centers

• Cross Cancer Institute (University of Alberta) — Edmonton
• Princess Margaret Cancer Centre — Toronto

Chile · 2 centers

• Centro de Estudios Clinicos SAGA — Providencia
• Bradford Hill- Centro de Investigación Clínica — Recoleta

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 2 centers

Center list to be confirmed — check the primary protocol.

Denmark · 1 center

Center list to be confirmed — check the primary protocol.

Netherlands · 1 center

Center list to be confirmed — check the primary protocol.

Singapore · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07195695 · 1479-0032 · U1111-1320-6149 · 2025-521284-12-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗