Trial: Beamion BCGC-1: A Study to Find a Suita…

Trial Details

Sponsor: Boehringer Ingelheim (industry)

Phase: 1/2

Start date: June 28, 2024

Planned enrollment: 582

Trial ID: NCT06324357

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Zongertinib (BI-1810631, NSC-854531)

Overview

Zongertinib (BI-1810631, NSC-854531) is an investigational, orally administered tyrosine kinase inhibitor (TKI) targeting HER2 mutations in advanced solid tumors, particularly non–small cell lung cancer (NSCLC). The drug has demonstrated promising efficacy and a manageable safety profile in early-phase clinical trials.

Mechanism of Action

Zongertinib selectively and irreversibly binds to the tyrosine kinase domain of HER2, inhibiting its activity while sparing wild-type epidermal growth factor receptor (EGFR). This selectivity aims to reduce EGFR-related adverse events commonly associated with other TKIs. (ascopubs.org)

Efficacy

In the Phase Ia portion of the Beamion LUNG-1 trial, zongertinib achieved a confirmed overall response rate (ORR) of 30% and a disease control rate (DCR) of 83% across various HER2-altered solid tumors. Specifically, among patients with NSCLC, the confirmed ORR was 35%, with a median duration of response of 12.7 months. (ascopubs.org)

The Phase Ib analysis of the same trial reported an ORR of 66.7% in Cohort 1, with tumor shrinkage observed in 94% of patients. In a randomized segment, the 120 mg and 240 mg daily doses resulted in ORRs of 72.4% and 78.2%, respectively, and DCRs of 95% and 100%. (worldpharmaceuticals.net)

Safety

Zongertinib has exhibited a manageable safety profile. In the Phase Ia study, treatment-related adverse events (TRAEs) occurred in 82% of patients, with 10% experiencing grade ≥3 TRAEs. The most common TRAEs included diarrhea (50%), rash (16%), and elevated liver enzymes. Notably, typical EGFR-related toxicities were infrequent, aligning with the drug's selective mechanism. (ascopubs.org)

In the Phase Ib cohort, any-grade TRAEs were reported in 66.7% of patients, with grade ≥3 events in 9.5%. The most common TRAEs were diarrhea (28.6%) and rash (21.4%). Dose-limiting toxicities included grade 3 febrile neutropenia and grade 4 immune thrombocytopenia. (targetedonc.com)

Regulatory Status

As of February 2025, the U.S. Food and Drug Administration (FDA) granted priority review to zongertinib for the treatment of adult patients with unresectable or metastatic NSCLC harboring HER2 mutations who have received prior systemic therapy. (pharmacytimes.com)

HealthScout AI Analysis

Goal: The primary goal of this trial is to determine the optimal tolerated dose and preliminary efficacy of zongertinib, a selective HER2 inhibitor, alone and in combination with established HER2-targeted agents, in patients with advanced HER2-positive cancers after failure of prior standard treatments.

Patients: The study includes adults (age 18 or above) with HER2-positive metastatic breast cancer or HER2-positive metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma who have experienced disease progression after standard therapy, have measurable disease, and are ECOG 0-1.

Design: This is a randomized, open-label, multicenter phase Ib/II trial. Phase Ib includes several dose-escalation cohorts to assess the safety and maximum tolerated dose of zongertinib in combination with other standard HER2-targeted regimens, while phase II uses randomized dose-optimization cohorts to further evaluate efficacy and safety.

Treatments: Investigational arms utilize zongertinib alone or in combination with trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), trastuzumab, and/or capecitabine. Zongertinib (BI 1810631) is an oral, selective, covalent HER2 tyrosine kinase inhibitor that spares EGFR, potentially resulting in fewer off-target toxicities. Early trials in HER2-mutant NSCLC reported objective response rates up to 74%, a disease control rate above 90%, and manageable toxicity (mainly low-grade diarrhea). Standard HER2-targeted agents such as T-DXd, T-DM1, trastuzumab, and capecitabine are also included according to current best practices for HER2-positive disease.

Outcomes: In phase Ib, primary endpoints are the occurrence of dose-limiting toxicities during the initial 21 days and objective response rate. In phase II, the primary outcome is objective response per RECIST 1.1. Secondary outcomes include progression-free survival, disease control, treatment-emergent adverse events, pharmacokinetics (Cmax and AUC), and patient-reported outcomes capturing symptomatic toxicities and treatment burden.

Burden on patient: Participant burden is moderate to high, consistent with a phase 1/2 trial setting. The trial involves extra clinic visits for dose escalation and safety monitoring, frequent imaging with CT or MRI for response assessment, and multiple blood draws for pharmacokinetic analyses. Tumor biopsies (preferably from non-irradiated sites) may be required for trial entry, and patient-reported outcomes are regularly collected. Combination regimens may increase the risk of overlapping toxicities, and close monitoring is necessary. Travel to specialized centers and frequent assessments will be required, resulting in a higher burden than standard of care.

Eligibility

Show Criteria

Inclusion Criteria:

* Signed and dated written Informed consent form (ICF) in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.

* 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 ICF.

* Documented Human epidermal growth factor receptor 2 overexpressing and/or amplified (HER2+), metastatic breast cancer (mBC) or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma (mGEAC).

* For dose optimization (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue.

* Documented investigator assessed progression.

* Recovered from any previous therapy-related toxicity to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at start of treatment (except for alopecia, stable sensory neuropathy, and hypothyroidism (patients on thyroid replacement therapy) which must be ≤ CTCAE Grade 2).

* Presence of at least one measurable lesion according to Response evaluation criteria in solid tumors (RECIST) 1.1, as determined by the local site investigator/radiology assessment.

* Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Further inclusion criteria apply.

Exclusion Criteria:

* Previous or concomitant malignancies other than the one treated in this trial within the previous 2 years, which require current systemic therapy except:

* effectively treated non-melanoma skin cancers

* effectively treated carcinoma in situ of the cervix

* effectively treated ductal carcinoma in situ

* other effectively treated malignancy that is considered cured by local treatment

* History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of ≥ III or IV, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator. Myocardial infarction (or troponin levels consistent with myocardial infarction within 28 days of randomization), stroke, or pulmonary embolism within 6 months prior to randomization.

* Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block.

* Mean resting corrected QT interval (QT interval corrected for heart rate by Fridericia´s formula (QTcF)) \>470 msec.

* Any factors that increase the risk of QT interval corrected for heart rate (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, personal or family history of long QT syndrome or unexplained sudden death under 40 years-of-age.

* Ejection fraction \<50% or the lower limit of normal of the institutional standard within 28 days prior to randomization.

* Women who are pregnant or nursing or who plan to become pregnant or nurse during the trial or within 7 months after the last dose of trial treatment with T-DXd, T-DM1, trastuzumab or capecitabine and trastuzumab.

Further exclusion criteria apply.

Sites (80)

Sort by distance to:

Brussels - UNIV Saint-Luc

Bruxelles, 1200, Belgium

[email protected] / 080049616

Status: Not yet recruiting

CHU UCL Namur - Site De Sainte-Elisabeth

Namur, 5000, Belgium

[email protected] / 080049616

Status: Recruiting

Centre Hospitalier Universitaire de Liège

Liege, 4000, Belgium

[email protected] / 080049616

Status: Recruiting

UZ Antwerpen

Libramont-Chevigny, 6800, Belgium

[email protected] / 080049616

Status: Recruiting

UZ Leuven

Leuven, 3000, Belgium

[email protected] / 080049616

Status: Recruiting

Edegem - UNIV UZ Antwerpen

Edegem, 2650, Belgium

[email protected] / 080049616

Status: Recruiting

The First Hospital of Jilin University

Changchun, 130021, China

[email protected] / 4001200553

Status: Not yet recruiting

Henan Cancer Hospital

Zhengzhou, 450003, China

[email protected] / 4001200553

Status: Recruiting

Tianjin Cancer Hospital

Tianjin, 300060, China

[email protected] / 4001200553

Status: Recruiting

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

[email protected] / 4001200553

Status: Recruiting

Jiangsu Province Hospital

Nanjing, 210029, China

[email protected] / 4001200553

Status: Recruiting

Harbin Medical University Cancer Hospital

Harbin, 150081, China

[email protected] / 4001200553

Status: Recruiting

Jilin Province Cancer Hospital

Changchun, 130012, China

[email protected] / 4001200553

Status: Recruiting

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

Hangzhou, 310000, China

[email protected] / 4001200553

Status: Recruiting

Institut de Cancérologie de Strasbourg

Strasbourg, 67200, France

[email protected] / 0805102354

Status: Not yet recruiting

INS Claudius Regaud IUCT-Oncopole

Toulouse, 31059, France

[email protected] / 0805102354

Status: Not yet recruiting

INS Paoli-Calmettes

Marseille Cedex 9, 13273, France

[email protected] / 0805102354

Status: Not yet recruiting

CTR Leon Berard

Lyon, 69008, France

[email protected] / 0805102354

Status: Not yet recruiting

CTR Georges-François Leclerc

Dijon, 21000, France

[email protected] / 0805102354

Status: Not yet recruiting

CTR François Baclesse

Caen, 14076, France

[email protected] / 0805102354

Status: Not yet recruiting

INS Bergonie

Bordeaux cedex, 33076, France

[email protected] / 0805102354

Status: Not yet recruiting

HOP Tenon

Paris, 75020, France

[email protected] / 0805102354

Status: Not yet recruiting

CTR Eugène Marquis

Rennes cedex, 35042, France

[email protected] / 0805102354

Status: Not yet recruiting

Institut de Cancérologie de l'Ouest

Saint Herblain, 44800, France

[email protected] / 0805102354

Status: Not yet recruiting

Evang. Kliniken Essen-Mitte gGmbh

Essen, 45136, Germany

[email protected] / 08007234742

Status: Not yet recruiting

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

[email protected] / 08007234742

Status: Not yet recruiting

Asklepios Kliniken GmbH & Co. KGaA

Hamburg, 22763, Germany

[email protected] / 08007234742

Status: Not yet recruiting

Istituto Clinico Humanitas

Rozzano, 20089, Italy

[email protected] / 800977373

Status: Recruiting

Istituto Scientifico Romagnolo

Meldola (fc), 47014, Italy

[email protected] / 800977373

Status: Not yet recruiting

Istituto Europeo di Oncologia

Milano, 20141, Italy

[email protected] / 800977373

Status: Recruiting

IRCCS San Raffaele

Milano, 20132, Italy

[email protected] / 800977373

Status: Recruiting

Istituto Di Candiolo

Candiolo (TO), 10060, Italy

[email protected] / 800977373

Status: Not yet recruiting

Az.Osp. Universitaria "Ospedali Riuniti"

Foggia, 71122, Italy

[email protected] / 800977373

Status: Not yet recruiting

Humanitas Istituto Clinico Catanese S.p.A.

Misterbianco (CT), 95045, Italy

[email protected] / 800977373

Status: Not yet recruiting

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Napoli, 80131, Italy

[email protected] / 800977373

Status: Not yet recruiting

Osaka International Cancer Institute

Osaka-shi, 541-8567, Japan

[email protected] / 0120201230

Status: Not yet recruiting

Kanagawa Cancer Center

Kanagawa, Yokohama, 241-8515, Japan

[email protected] / 0120201230

Status: Not yet recruiting

National Cancer Center Hospital East

Kashiwa-shi, 277-8577, Japan

[email protected] / 0120201230

Status: Recruiting

Kyoto University Hospital

Kyoto, Kyoto, 606-8507, Japan

[email protected] / 0120201230

Status: Recruiting

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550, Japan

[email protected] / 0120201230

Status: Recruiting

Aichi Cancer Center Hospital

Aichi, Nagoya, 464-8681, Japan

[email protected] / 0120201230

Status: Not yet recruiting

Hakuaikai Sagara Hospital

Kagoshima-shi, 892-0833, Japan

[email protected] / 0120201230

Status: Not yet recruiting

Tokai University Hospital

Kanagawa, Isehara, 259-1193, Japan

[email protected] / 0120201230

Status: Not yet recruiting

CHA Bundang Medical Center

Seongnam-si, 13496, Korea, Republic of

[email protected] / 0808802084

Status: Not yet recruiting

Severance Hospital, Yonsei University Health System

Seoul, 03722, Korea, Republic of

[email protected] / 0808802084

Status: Not yet recruiting

Asan Medical Center

Seoul, 05505, Korea, Republic of

[email protected] / 0808802084

Status: Not yet recruiting

Seoul National University Hospital

Seoul, 3080, Korea, Republic of

[email protected] / 0808802084

Status: Not yet recruiting

Clínica Universidad de Navarra - Madrid

Madrid, 28022, Spain

[email protected] / 900876092

Status: Not yet recruiting

Hospital Teresa Herrera

A Coruña, 15006, Spain

[email protected] / 900876092

Status: Not yet recruiting

Hospital del Mar

Barcelona, 08003, Spain

[email protected] / 900876092

Status: Not yet recruiting

Hospital Vall d'Hebron

Barcelona, 08035, Spain

[email protected] / 900876092

Status: Recruiting

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

[email protected] / 900876092

Status: Recruiting

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 8906, Spain

[email protected] / 900876092

Status: Not yet recruiting

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

[email protected] / 900876092

Status: Not yet recruiting

Fundación Jiménez Díaz

Madrid, 28040, Spain

[email protected] / 900876092

Status: Recruiting

Hospital Clínico San Carlos

Madrid, 28040, Spain

[email protected] / 900876092

Status: Not yet recruiting

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

[email protected] / 900876092

Status: Not yet recruiting

Hospital La Paz

Madrid, 28046, Spain

[email protected] / 900876092

Status: Not yet recruiting

CIO Clara Campal

Madrid, 28050, Spain

[email protected] / 900876092

Status: Recruiting

Hospital Virgen Macarena

Sevilla, 41009, Spain

[email protected] / 900876092

Status: Not yet recruiting

Instituto Valenciano de Oncología

Valencia, 46009, Spain

[email protected] / 900876092

Status: Not yet recruiting

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

[email protected] / 08000514022

Status: Not yet recruiting

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

[email protected] / 08000514022

Status: Not yet recruiting

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

[email protected] / 08000514022

Status: Not yet recruiting

University of California Irvine

Orange, California, 92868, United States

[email protected] / 833-602-2368

Status: Recruiting

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

[email protected] / 833-602-2368

Status: Recruiting

The Oncology Institute of Hope and Innovation

Cerritos, California, 90703, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Sharp Memorial Hospital

San Diego, California, 92123, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

[email protected] / 833-602-2368

Status: Recruiting

Community Health Network

Indianapolis, Indiana, 46250, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Tennessee Oncology, Pllc

Nashville, Tennessee, 37203, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Baptist Cancer Center - Memphis

Memphis, Tennessee, 38120, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

The Methodist Hospital Research Institute

Houston, Texas, 77030, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

[email protected] / 833-602-2368

Status: Not yet recruiting

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Zongertinib (BI-1810631, NSC-854531)

Overview

Mechanism of Action

Efficacy

Safety

Regulatory Status

Further Reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (80)

Brussels - UNIV Saint-Luc

CHU UCL Namur - Site De Sainte-Elisabeth

Centre Hospitalier Universitaire de Liège

UZ Antwerpen

UZ Leuven

Edegem - UNIV UZ Antwerpen

The First Hospital of Jilin University

Henan Cancer Hospital

Tianjin Cancer Hospital

Fudan University Shanghai Cancer Center

Jiangsu Province Hospital

Harbin Medical University Cancer Hospital

Jilin Province Cancer Hospital

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

Institut de Cancérologie de Strasbourg

INS Claudius Regaud IUCT-Oncopole

INS Paoli-Calmettes

CTR Leon Berard

CTR Georges-François Leclerc

CTR François Baclesse

INS Bergonie

HOP Tenon

CTR Eugène Marquis

Institut de Cancérologie de l'Ouest

Evang. Kliniken Essen-Mitte gGmbh

Universitätsklinikum Carl Gustav Carus Dresden

Asklepios Kliniken GmbH & Co. KGaA

Istituto Clinico Humanitas

Istituto Scientifico Romagnolo

Istituto Europeo di Oncologia

IRCCS San Raffaele

Istituto Di Candiolo

Az.Osp. Universitaria "Ospedali Riuniti"

Humanitas Istituto Clinico Catanese S.p.A.

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Osaka International Cancer Institute

Kanagawa Cancer Center

National Cancer Center Hospital East

Kyoto University Hospital

Japanese Foundation for Cancer Research

Aichi Cancer Center Hospital

Hakuaikai Sagara Hospital

Tokai University Hospital

CHA Bundang Medical Center

Severance Hospital, Yonsei University Health System

Asan Medical Center

Seoul National University Hospital

Clínica Universidad de Navarra - Madrid

Hospital Teresa Herrera

Hospital del Mar

Hospital Vall d'Hebron

Hospital Clínic de Barcelona

Hospital Duran i Reynals

Hospital General Universitario Gregorio Marañón

Fundación Jiménez Díaz

Hospital Clínico San Carlos

Hospital Universitario 12 de Octubre

Hospital La Paz

CIO Clara Campal

Hospital Virgen Macarena

Instituto Valenciano de Oncología

St Bartholomew's Hospital

St James's University Hospital

Nottingham University Hospitals NHS Trust

University of California Irvine

Valkyrie Clinical Trials