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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04886804




Registration number
NCT04886804
Ethics application status
Date submitted
4/05/2021
Date registered
14/05/2021
Date last updated
1/11/2024

Titles & IDs
Public title
A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)
Scientific title
Beamion LUNG-1: An Open Label, Phase I Dose Escalation Trial, With Dose Confirmation and Expansion, of Zongertinib (BI 1810631) as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations
Secondary ID [1] 0 0
2020-004563-47
Secondary ID [2] 0 0
1479-0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasm Metastasis 0 0
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - zongertinib

Experimental: Phase Ia - Dose escalation part - Consecutive cohorts of patients treated with escalating doses of BI 1810631 monotherapy.

Experimental: Phase Ib - Dose expansion part: Cohort 1 -

Experimental: Phase Ib - Dose expansion part: Cohort 2 -

Experimental: Phase Ib - Dose expansion part: Cohort 3 -

Experimental: Phase Ib - Dose expansion part: Cohort 4 -

Experimental: Phase Ib - Dose expansion part: Cohort 5 -

Experimental: Phase Ib - Dose expansion part: Cohort 6 - Cohort only in the United States of America (USA)

Experimental: Phase Ib - Dose expansion part: Cohort 7 - Cohort only in Japan


Treatment: Drugs: zongertinib
zongertinib
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ia: Maximum Tolerated Dose (MTD)
Timepoint [1] 0 0
At the end of Cycle 1 (each cycle is 21 days).
Primary outcome [2] 0 0
Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) in the MTD evaluation period
Timepoint [2] 0 0
At the end of Cycle 1 (each cycle is 21 days).
Primary outcome [3] 0 0
Phase Ib - Cohorts 1, 2 and 5 : Objective response (OR) as assessed by central independent review
Timepoint [3] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Primary outcome [4] 0 0
Phase Ib - Cohorts 3, 6 and 7: Objective response according to RECIST 1.1 by investigator assessment
Timepoint [4] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Primary outcome [5] 0 0
Phase Ib: Cohort 4: Objective response according to Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) by central independent review
Timepoint [5] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [1] 0 0
Phase Ia: Number of patients experiencing DLTs during the entire treatment period
Timepoint [1] 0 0
From the start of the trial treatment until end of month 8, up to 8 months.
Secondary outcome [2] 0 0
Phase Ia: Maximum measured concentration of zongertinib in plasma (Cmax)
Timepoint [2] 0 0
On day 1 and on day 15 of Cycle 1 (each cycle is 21 days).
Secondary outcome [3] 0 0
Phase Ia: Area under the concentration-time curve of zongertinib in plasma (AUC0-t2)
Timepoint [3] 0 0
On day 1 and on day 15 of Cycle 1 (each cycle is 21 days).
Secondary outcome [4] 0 0
Phase Ib - Cohorts 1, 2 and 5: Duration of objective response (DoR) according to RECIST 1.1
Timepoint [4] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [5] 0 0
Phase Ib - Cohorts 1, 2 and 5: Disease control (DC)
Timepoint [5] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [6] 0 0
Phase Ib - Cohorts 1, 2 and 5: Progression-free survival (PFS)
Timepoint [6] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [7] 0 0
Phase Ib - Cohorts 1, 2 and 5: Objective response according to response assessment in neuro-oncology for brain metastases (RANO-BM) criteria as assessed by central independent review for patients with central nervous system (CNS) lesions at baseline
Timepoint [7] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [8] 0 0
Phase Ib - Cohorts 1, 2 and 5: Disease control according to RANO-BM criteria as assessed by central independent review for patients with CNS lesions at baseline
Timepoint [8] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [9] 0 0
Phase Ib - Cohorts 3, 6 and 7: Duration of objective response according to RECIST 1.1 by investigator assessment
Timepoint [9] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [10] 0 0
Phase Ib - Cohorts 3, 6 and 7: Disease control according to RECIST 1.1 as assessed by the investigator
Timepoint [10] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [11] 0 0
Phase Ib - Cohorts 3, 6 and 7: Progression-free survival according to RECIST 1.1 as assessed by the investigator
Timepoint [11] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [12] 0 0
Phase Ib - Cohorts 3, 6 and 7: Objective response according to RANO-BM criteria as assessed by the investigator for patients with CNS lesions at baseline
Timepoint [12] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [13] 0 0
Phase Ib - Cohorts 3, 6 and 7: Disease control according to RANO-BM criteria as assessed by the investigator for patients with CNS lesions at baseline
Timepoint [13] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [14] 0 0
Phase Ib - Cohort 4: Duration of objective response (DoR) according to RANO-BM by central independent review
Timepoint [14] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [15] 0 0
Phase Ib - Cohort 4: Disease control (DC) according to RANO-BM by central independent review
Timepoint [15] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [16] 0 0
Phase Ib - Cohort 4: Progression-free survival (PFS) according to RANO-BM as assessed by central independent review
Timepoint [16] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [17] 0 0
Phase Ib - Cohort 4: OR according to RECIST 1.1 by central independent review
Timepoint [17] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [18] 0 0
Phase Ib - Cohort 4: Duration of OR according to RECIST 1.1 by central independent review
Timepoint [18] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [19] 0 0
Phase Ib - Cohort 4: DC according to RECIST 1.1 by central independent review
Timepoint [19] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [20] 0 0
Phase Ib - Cohort 4: PFS according to RECIST 1.1 as assessed by central independent review
Timepoint [20] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [21] 0 0
Phase Ib - All Cohorts: Number of patients experiencing DLTs during the entire treatment period
Timepoint [21] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.
Secondary outcome [22] 0 0
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) physical functioning domain score
Timepoint [22] 0 0
Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
Secondary outcome [23] 0 0
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score
Timepoint [23] 0 0
Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
Secondary outcome [24] 0 0
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in EORTC item List 46 (IL46) score
Timepoint [24] 0 0
Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
Secondary outcome [25] 0 0
Phase Ib - All cohorts: Overall survival (OS), defined as time from first treatment administration until death from any cause
Timepoint [25] 0 0
From the start of the trial treatment until end of month 12, up to 12 months.

Eligibility
Key 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 and 7) .
* 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.
* 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)1 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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. For Phase Ib only: Previous treatment with any HER2 targeted treatment.
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/01/2028
Actual
Sample size
Target
554
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Macquarie University - Macquarie Park
Recruitment postcode(s) [1] 0 0
2109 - Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Austria
State/province [11] 0 0
Linz
Country [12] 0 0
Belgium
State/province [12] 0 0
Anderlecht/Brussels-Capital
Country [13] 0 0
China
State/province [13] 0 0
Beijing
Country [14] 0 0
China
State/province [14] 0 0
Changchun
Country [15] 0 0
China
State/province [15] 0 0
Fuzhou
Country [16] 0 0
China
State/province [16] 0 0
Guangzhou
Country [17] 0 0
China
State/province [17] 0 0
Hangzhou
Country [18] 0 0
China
State/province [18] 0 0
Harbin
Country [19] 0 0
China
State/province [19] 0 0
Nanning
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
China
State/province [21] 0 0
Tianjin
Country [22] 0 0
China
State/province [22] 0 0
Wuhan
Country [23] 0 0
China
State/province [23] 0 0
Xiamen
Country [24] 0 0
China
State/province [24] 0 0
Zhengzhou
Country [25] 0 0
France
State/province [25] 0 0
Bron
Country [26] 0 0
France
State/province [26] 0 0
Lyon
Country [27] 0 0
France
State/province [27] 0 0
Marseille
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
France
State/province [29] 0 0
Rennes
Country [30] 0 0
France
State/province [30] 0 0
Villejuif
Country [31] 0 0
Germany
State/province [31] 0 0
Augsburg
Country [32] 0 0
Germany
State/province [32] 0 0
Dresden
Country [33] 0 0
Germany
State/province [33] 0 0
Gießen
Country [34] 0 0
Germany
State/province [34] 0 0
Köln
Country [35] 0 0
Germany
State/province [35] 0 0
Oldenburg
Country [36] 0 0
Hong Kong
State/province [36] 0 0
Hong Kong
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Kfar Saba
Country [39] 0 0
Israel
State/province [39] 0 0
Tel Aviv
Country [40] 0 0
Israel
State/province [40] 0 0
Tel Hashomer
Country [41] 0 0
Italy
State/province [41] 0 0
Candiolo (TO)
Country [42] 0 0
Italy
State/province [42] 0 0
Napoli
Country [43] 0 0
Italy
State/province [43] 0 0
Parma
Country [44] 0 0
Japan
State/province [44] 0 0
Chiba, Kashiwa
Country [45] 0 0
Japan
State/province [45] 0 0
Ehime, Matsuyama
Country [46] 0 0
Japan
State/province [46] 0 0
Hiroshima, Hiroshima
Country [47] 0 0
Japan
State/province [47] 0 0
Miyagi, Sendai
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka, Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Shizuoka, Hamamatsu
Country [50] 0 0
Japan
State/province [50] 0 0
Tokyo, Chuo-ku
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Cheongju-si
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Seongnam
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Seoul
Country [54] 0 0
Netherlands
State/province [54] 0 0
Amsterdam
Country [55] 0 0
Netherlands
State/province [55] 0 0
Leiden
Country [56] 0 0
Portugal
State/province [56] 0 0
Porto
Country [57] 0 0
Singapore
State/province [57] 0 0
Singapore
Country [58] 0 0
Spain
State/province [58] 0 0
Barcelona
Country [59] 0 0
Spain
State/province [59] 0 0
L'Hospitalet de Llobregat
Country [60] 0 0
Spain
State/province [60] 0 0
Madrid
Country [61] 0 0
Spain
State/province [61] 0 0
Malaga
Country [62] 0 0
Spain
State/province [62] 0 0
Valencia
Country [63] 0 0
Sweden
State/province [63] 0 0
Stockholm
Country [64] 0 0
United Kingdom
State/province [64] 0 0
London
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04886804
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Boehringer Ingelheim
Address 0 0
Country 0 0
Phone 0 0
1-800-243-0127
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04886804