Beamion 44: A Study to Test How Well Zongertinib is Tolerated by People With Advanced Non-small Cell Lung Cancer With HER2 Mutations When Given in Combination With Chemotherapy With or Without Pembrolizumab

Official title

Beamion 44: A Randomized, Open-label, Multi-center Phase IIa Platform Trial to Evaluate the Safety and Tolerability of Zongertinib Plus Platinum-based Doublet Chemotherapy With or Without Pembrolizumab (and Potential Other Combinations) in Treatment-naïve Patients With Locally Advanced/Metastatic Non-squamous NSCLC With Activating HER2 Mutations

Overview

This study is open to adults with a type of lung cancer called HER2-mutant non-squamous non-small cell lung cancer (NSCLC) that is advanced or has spread. People who have a tumor with a HER2 mutation and have not received previous treatment for their lung cancer can participate in the study. The purpose of this study is to find out how well a medicine called zongertinib is tolerated in people with this type of lung cancer, when combined with chemotherapy, with or without pembrolizumab. Zongertinib works by targeting and blocking HER2, a protein involved in cancer cell growth. Participants are put into two groups randomly, which means by chance. One group gets zongertinib tablets combined with platinum-based chemotherapy. The other group gets the same treatment plus an additional medicine called pembrolizumab. Chemotherapy and pembrolizumab are given as an infusion into a vein. Participants take zongertinib by mouth once a day, while chemotherapy is given every 3 weeks for up to 3 months, followed by maintenance treatment for up to 2 years. Pembrolizumab is given every 3 weeks for up to 2 years. This study does not have a fixed duration. Participants can receive some of the study treatments for up to about 2 years and may continue to take zongertinib as long as they benefit from treatment and can tolerate it. During this time, they visit the study site regularly. Doctors regularly check the size of the tumor and whether it has spread. They also monitor participants' health and take note of any unwanted effects.

Interventions

• Drug Zongertinib
  Zongertinib
• Drug Cisplatin
  Cisplatin
• Drug Carboplatin
  Carboplatin
• Drug Pemetrexed
  Pemetrexed
• Drug Pembrolizumab
  Pembrolizumab

Primary outcome measures

• Occurrence of discontinuation and/or prolonged interruption (>7 days) of zongertinib due to treatment-related adverse events (AEs) in the first 2 cycles of treatment [Time frame: up to 6 weeks]

Secondary outcome measures (10)

• Occurrence of serious adverse events (SAE) during the on-treatment period [Time frame: up to 1.5 years]
• Occurrence of dose reduction of zongertinib [Time frame: up to 1.5 years]
• Occurrence of discontinuation and/or prolonged interruption (>7 days) of zongertinib due to treatment-related AEs during the on-treatment period [Time frame: up to 1.5 years]
• Occurrence of Grade ≥3 non-hematological AE during the on-treatment period [Time frame: up to 1.5 years]
• Occurrence of combination limiting toxicities (CLTs) during the on-treatment period [Time frame: up to 1.5 years]
• Objective response (OR) according to Response evaluation criteria in solid tumors (RECIST) 1.1 as assessed by the investigator [Time frame: up to 1.5 years]
• Time to OR, defined as the time from date of randomization to first documented confirmed CR or PR among patients with OR as determined by investigator assessment per RECIST 1.1 [Time frame: up to 1.5 years]
• Duration of OR (DoR), defined as the time from first documented confirmed CR or PR until disease progression or death among patients with OR as determined by investigator assessment per RECIST 1.1 [Time frame: up to 1.5 years]
• Progression-free survival (PFS), defined as the time from randomization until tumor progression according to RECIST 1.1 as assessed by the investigator, or death from any cause, whichever occurs earlier [Time frame: up to 1.5 years]
• Time on treatment (ToT), defined as the time from first dose of study treatment until zongertinib treatment discontinuation or death [Time frame: up to 1.5 years]

Eligibility criteria

Inclusion criteria

• Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF)
• Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous non-small cell lung cancer (NSCLC)
• Documented activating human epidermal growth factor receptor 2 (HER2) mutation as per existing local lab result
• An archival tumor tissue sample must be submitted to the central laboratory after randomization to retrospectively confirm the HER2 status
• Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease
• Presence of at least one measurable non-Central Nervous System (CNS) lesion according to response evaluation criteria in solid tumors (RECIST) 1.1
• Eligible to receive treatment with the selected platinum based doublet chemotherapy and pembrolizumab in accordance with the summary of product characteristics (SmPC)/Product Information
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 Further inclusion criteria apply.

Exclusion criteria

• Tumors with targetable alterations with approved available therapy
• Presence or history of leptomeningeal disease
• Radiotherapy within 4 weeks prior to treatment start with exception of palliative radiotherapy to regions other than the chest if completed at least 2 weeks prior to treatment start
• Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening
• Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug
• Previous therapy with a HER2-directed agent
• History or presence of cardiovascular abnormalities which are considered as clinically relevant by the investigator. Myocardial infarction, stroke, or pulmonary embolism within 6 months prior to randomization 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

Australia · 3 centers

• Royal North Shore Hospital — St Leonards
• Cabrini Health — Malvern
• Fiona Stanley Hospital — Murdoch

South Korea · 3 centers

• Severance Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Spain · 3 centers

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Virgen del Rocío — Seville

China · 2 centers

• Guangdong Provincial People's Hospital — Guangzhou
• Shanghai Geriatric Medical Center — Shanghai

France · 2 centers

• CTR Leon Berard — Lyon
• INS Curie — Paris

Germany · 2 centers

• Universitätsklinikum Köln (AöR) — Cologne
• Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg — Heidelberg

Japan · 2 centers

• Kindai University Hospital — Osaka, Sakai
• National Cancer Center Hospital — Tokyo, Chuo-ku

Identifiers

NCT: NCT07486817 · 1479-0044 · 2025-523567-38-00 · U1111-1327-3020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗