Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)
The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumours with changes in the HER2 gene) for whom previous treatment was not successful.
The second part is open to people with non-small cell lung cancer with a specific mutation in the HER2 gene.
The purpose of the first study part is to find the highest dose of a medicine called zongertinib the participants can tolerate. Once this dose is found, it will be used in the second study part to test whether zongertinib can make tumours shrink.
In this study, zongertinib is given to people for the first time. Participants take zongertinib as tablets once a day or twice a day.
The participants are in the study for as long as they benefit from and can tolerate treatment.
Study doctors regularly check the participants' health and monitor the tumours. The doctors also take note of any unwanted effects that could have been caused by zongertinib.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Phase Ia: Maximum Tolerated Dose (MTD) — At the end of Cycle 1 (each cycle is 21 days). Maximum tolerated dose is defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal to or above 33% during the MTD evaluation period in any studied regimen.
Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) in the MTD evaluation period — At the end of Cycle 1 (each cycle is 21 days).
Phase Ib - Cohorts 1, 2 and 5 : Objective response (OR) as assessed by central independent review — From the start of the trial treatment until end of month 12, up to 12 months. OR is defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, from the first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
Phase Ib - Cohorts 3, 6, 7, 8, and 9: Objective response according to RECIST 1.1 by investigator assessment — From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib: Cohort 4: Objective response according to Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) by central independent review — From the start of the trial treatment until end of month 12, up to 12 months.
Trial sites (85)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
Precision NextGen Oncology
Beverly Hills
California
City of Hope-Duarte-56419
Duarte
California
City of Hope - Seacliff
Huntington Beach
California
City of Hope-Irvine-69674
Irvine
California
Valkyrie Clinical Trials
Los Angeles
California
University of California Irvine
Orange
California
University of California Davis
Sacramento
California
Georgetown University
Washington D.C.
District of Columbia
Holy Cross Hospital-Fort Lauderdale-57892
Fort Lauderdale
Florida
Winship Cancer Institute
Atlanta
Georgia
Hawaii Cancer Care - Honolulu
Honolulu
Hawaii
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York
New York
Duke University Medical Center
Durham
North Carolina
Cleveland Clinic
Cleveland
Ohio
Sarah Cannon Research Institute-Nashville-48456
Nashville
Tennessee
Mary Crowley Cancer Research Center
Dallas
Texas
The University of Texas MD Anderson Cancer Center
Houston
Texas
Virginia Cancer Specialists, PC
Fairfax
Virginia
Fred Hutchinson Cancer Research Center
Seattle
Washington
Macquarie University
Macquarie Park
New South Wales
Ordensklinikum Linz GmbH
Linz
Austria
Brussels - HOSP Jules Bordet
Anderlecht/Brussels-Capital
Belgium
Beijing Cancer Hospital
Beijing
China
Jilin Province Cancer Hospital
Changchun
China
The First Hospital of Jilin University
Changchun
China
Fujian Cancer Hospital
Fuzhou
China
Guangdong Provincial People's Hospital
Guangzhou
China
The First Affiliated Hospital, Zhejiang University
Hangzhou
China
Zhejiang Cancer Hospital
Hangzhou
China
Harbin Medical University Cancer Hospital
Harbin
China
The Affiliated Cancer Hospital, Guangxi Medical University
Nanning
China
Shanghai Chest Hospital
Shanghai
China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan
China
Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
Wuhan
China
First Affiliated Hospital of Xiamen University
Xiamen
China
Henan Cancer Hospital
Zhengzhou
China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou
China
Hôpital Louis Pradel
Bron
France
CTR Leon Berard
Lyon
France
+ 45 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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