New pill shows promise against Hard-to-Treat HER2 cancers

NCT ID NCT04886804

Disease control Sponsor: Boehringer Ingelheim Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Aug 21, 2026 · Updated 6 times

Summary

This early-stage trial tests a new daily pill, zongertinib, in adults with advanced cancers that have HER2 gene changes, including non-small cell lung cancer. The first part finds the safest dose; the second checks if it shrinks tumors. Participants stay on the drug as long as it helps and side effects are manageable.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

About 554 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jul 2021

Expected to finish

Aug 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must show presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. * Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (ECOG=2 only for Cohorts 6, 7 and 9) . * Availability and patient willingness to provide a sample of tumour for confirmation of the patient´s Human epidermal growth factor receptor 2 (HER2) status. This sample can be archival material obtained at any time prior to study enrollment. * Patient willing and able to comply with the protocol requirements for tumour biopsies (biopsies from brain metastases are not allowed). * Adequate organ function defined as all of the following: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (≥ 1.5 x 10\^3/μL) (≥ 1500/mm\^3); haemoglobin ≥ 9.0 g/dL (≥ 90 g/L) (≥ 5.6 mmol/L); platelets ≥ 100 x 10\^9/L (100 x 10\^3/μL) (100 x 10\^3/mm3) without the use of hematopoietic growth factors within 4 weeks of start of trial medication. * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN. * Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min - calculated using Chronic Kidney Disease Epidemiology (CKD-EPI) formula (≥ 30 mL/min/1.73m² for cohorts 6, 8, and 9). * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases. * Alkaline Phosphatase \< 5 x ULN. * 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) * Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator. * At least 18 years of age at the time of consent or over the legal age of consent in countries where that is greater than 18 years. * Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. * Male or female patients. Women of childbearing potential (WOCBP) and men who are able to father a child must be ready and able to use highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. Additional inclusion criteria for Phase Ia * Patients with a documented diagnosis of HER2 aberration: overexpression OR gene amplification OR non-synonymous somatic mutation OR gene rearrangement involving HER2 or Neuregulin 1 (NRG1) * Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted, or not be a suitable candidate for, available treatment options known to prolong survival for their disease Additional inclusion criteria for Phase Ib - Cohort 1 only * Non-squamous non-small cell lung cancer (NSCLC) patients with documented human epidermal growth factor receptor 2 (HER2) mutation in the tyrosine kinase domain (TKD) as per local lab results. * Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. Patients with non-squamous NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care. Additional inclusion criteria for Phase Ib - Cohort 2 only * Non-squamous NSCLC patient with a documented HER2 mutation in the tyrosine kinase domain (TKD) as per local lab results. * Treatment naïve for non-squamous NSCLC. Additional inclusion criteria for Phase Ib - Cohort 3 only * NSCLC Patient with a documented HER2 mutation outside of the tyrosine kinase domain (TKD) as per local lab results or squamous NSCLC patient with mutation in the TKD as per local lab results. * Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care. Additional inclusion criteria for Phase Ib - Cohort 4 only * NSCLC patients with documented HER2 mutation in the TKD as per local lab results. * NSCLC patients who are either treatment naïve or who had received any prior line of treatment, in the advanced/metastatic setting. Patients with NSCLC harboring additional genomic aberrations for which approved targeted therapy is available as standard of care. * Patient with active brain metastases who are not eligible for immediate local therapy, as per investigator evaluation. Additional inclusion criteria for Phase Ib - Cohort 5 only * Non-squamous NSCLC patients with documented HER2 mutation in the TKD as per local lab results. * Patient should have received, in the advanced/metastatic setting, at least one line of systemic therapy that includes a platinum-based combination chemotherapy and should have been treated with previous HER2 directed antibody-drug conjugates (ADC) in the same advanced/metastatic setting and developed disease progression recurrence during or after completing this therapy. Patients with NSCLC harboring additional genomic aberrations for which approved targeted therapy is available as standard of care. Additional inclusion criteria for Phase Ib - Cohort 6 only * Non-squamous NSCLC patient with documented HER2 mutation in the TKD as per local lab results. * Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. * Patient without active brain metastases or patient with active brain metastases who are not eligible for immediate local therapy, as per investigator evaluation. * Patient who is not eligible for any other recruiting cohort. Additional inclusion criteria for Phase Ib - Cohort 7 only * Non-squamous NSCLC patient with documented HER2 mutation in the TKD as per local lab results. * Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. * Patient without active brain metastases or patient with active brain metastases who are not eligible for immediate local therapy, as per investigator evaluation. * Patient who is not eligible for any other recruiting cohort. Additional inclusion criteria for Phase Ib - Cohort 8 only * Treatment naïve for NSCLC * NSCLC (adenocarcinoma or squamous) patient with documented HER2 mutation in the tyrosine kinase domain (TKD) or non-squamous NSCLC with a documented HER2 mutation in the non tyrosine kinase domain (non TKD) as per local lab results Additional inclusion criteria for Phase Ib - Cohort 9 only * Non-squamous NSCLC patient with documented HER2 mutation in the TKD as per local lab results. * Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care. Further inclusion criteria apply. Exclusion Criteria: * Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to first trial treatment or planned within 6 months after screening * Previous or concomitant malignancies other than the one treated in this trial within the last 2 years, 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. * Treatment with a systemic anti-cancer therapy or investigational drug within 21 days or 5 half-lives (whichever is shorter) of the first treatment with the study medication * Patients who must or wish to continue the intake of restricted medication or any drug considered likely to interfere with the safe conduct of the trial * Previous treatment with zongertinib. * Radiotherapy within 2 weeks prior to first study treatment, except palliative radiotherapy to regions other than the chest, which is allowed up to 1 week prior to first study treatment. Further exclusion criteria apply.

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Conditions

The condition(s) this trial relates to.

metastatic neoplasm Neoplasm Metastasis non-small cell lung carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Neoplasm metastasis Non-small cell lung cancer

Contacts and locations

Locations

Asan Medical Center

Seoul, 05505, South Korea
Azienda Ospedaliera Unversitaria di Parma

Parma, 43100, Italy
Beijing Cancer Hospital

Beijing, 100036, China
Brussels - HOSP Jules Bordet

Anderlecht/Brussels-Capital, 1070, Belgium
CTR Leon Berard

Lyon, 69373, France
Chungbuk National University Hospital

Chungju, 28644, South Korea
City of Hope - Seacliff

Huntington Beach, California, 92648, United States
City of Hope-Duarte-56419

Duarte, California, 91010, United States
City of Hope-Irvine-69674

Irvine, California, 92618, United States
Cleveland Clinic

Cleveland, Ohio, 44195, United States
Duke University Medical Center

Durham, North Carolina, 27710, United States
First Affiliated Hospital of Xiamen University

Xiamen, 361003, China
Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States
Fujian Cancer Hospital

Fuzhou, 350014, China
Georgetown University

Washington D.C., District of Columbia, 20007, United States
Guangdong Provincial People's Hospital

Guangzhou, 510080, China
HOP Pontchaillou

Rennes, 35000, France
HOP Timone

Marseille, 13385, France
Hamamatsu University Hospital

Shizuoka, Hamamatsu, 431-3192, Japan
Hammersmith Hospital

London, W12 0HS, United Kingdom
Harbin Medical University Cancer Hospital

Harbin, 150081, China
Hawaii Cancer Care - Honolulu

Honolulu, Hawaii, 96813, United States
Henan Cancer Hospital

Zhengzhou, 450008, China
Hiroshima University Hospital

Hiroshima, Hiroshima, 734-8551, Japan
Holy Cross Hospital-Fort Lauderdale-57892

Fort Lauderdale, Florida, 33308, United States
Hospital CUF Porto

Porto, 4100-180, Portugal
Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain
Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain
Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain
Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain
Hospital Universitario 12 de Octubre

Madrid, 28041, Spain
Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain
Hôpital Louis Pradel

Bron, 69677, France
INS Curie

Paris, 75005, France
Institut Gustave Roussy

Villejuif, 94805, France
Istituto Di Candiolo

Candiolo (TO), 10060, Italy
Istituto Nazionale IRCCS Tumori Fondazione Pascale

Naples, 80131, Italy
Jilin Province Cancer Hospital

Changchun, 130012, China
Justus-Liebig Universität Gießen

Giessen, 35392, Germany
Karolinska Universitetssjukhuset Solna

Stockholm, 171 76, Sweden
Kindai University Hospital

Osaka, Sakai, 590-0197, Japan
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States
Leids Universitair Medisch Centrum (LUMC)

Leiden, 2333 ZA, Netherlands
Macquarie University

Macquarie Park, New South Wales, 2109, Australia
Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States
Meir Medical Center

Kfar Saba, 44281, Israel
National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan
National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577, Japan
National Cancer Centre Singapore

Singapore, 169610, Singapore
National University Hospital-Singapore-22806

Singapore, 119228, Singapore
Nederlands Kanker Instituut

Amsterdam, 1066 CX, Netherlands
Ordensklinikum Linz GmbH

Linz, 4020, Austria
Osaka International Cancer Institute

Osaka, Osaka, 541-8567, Japan
Pius-Hospital, Oldenburg

Oldenburg, 26121, Germany
Precision NextGen Oncology

Beverly Hills, California, 90212, United States
Prince of Wales Hospital-Hong Kong-20715

Hong Kong, 999077, Hong Kong
Queen Mary Hospital

Hong Kong, Hong Kong
Rambam Medical Center

Haifa, 3109601, Israel
Samsung Medical Center

Seoul, 06351, South Korea
Sarah Cannon Research Institute-Nashville-48456

Nashville, Tennessee, 37203, United States
Seoul National University Bundang Hospital

Seongnam, 13620, South Korea
Severance Hospital

Seoul, 03722, South Korea
Shanghai Chest Hospital

Shanghai, 200030, China
Shikoku Cancer Center

Ehime, Matsuyama, 791-0280, Japan
Sourasky Medical Center

Tel Aviv, 6423906, Israel
Technische Universität Dresden

Dresden, 01307, Germany
The Affiliated Cancer Hospital, Guangxi Medical University

Nanning, 530021, China
The Chaim Sheba Medical Center Tel HaShomer

Tel Litwinsky, 52621, Israel
The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450052, China
The First Affiliated Hospital, Zhejiang University

Hangzhou, 310003, China
The First Hospital of Jilin University

Changchun, 130021, China
The Royal Marsden Hospital, Chelsea

London, SW3 6JJ, United Kingdom
The Royal Marsden Hospital, Sutton

Sutton, SM2 5PT, United Kingdom
The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States
Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T

Wuhan, 430030, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430022, China
University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States
University of California Davis

Sacramento, California, 95817, United States
University of California Irvine

Orange, California, 92868, United States
Universitätsklinikum Augsburg

Augsburg, 86156, Germany
Universitätsklinikum Köln (AöR)

Cologne, 50937, Germany
Valkyrie Clinical Trials

Los Angeles, California, 90067, United States
Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States
Winship Cancer Institute

Atlanta, Georgia, 30322, United States
Zhejiang Cancer Hospital

Hangzhou, 310022, China

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