BEAMION Lung-2: A study to test whether zongertinib (BI 1810631) helps people with advanced non-small cell lung cancer with HER2 mutations compared with standard treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Jun 2024 → ongoing

Decision date (initial)

2024-03-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-504308-27-00

WHO UTN

U1111-1294-1407

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective of the trial is to show superiority of zongertinib (BI 1810631) over SoC (pembrolizumab plus platinum-pemetrexed chemotherapy) based on the hazard ratio of progression-free survival (PFS) in patients diagnosed with unresectable, locally advanced or metastatic histologically documented non-squamous NSCLC with HER2 TKD mutations who have not received any systemic treatment in this setting. The primary endpoint is PFS per RECIST 1.1 determined by central independent review.

Secondary objectives 2

1. The key secondary objectives are to show superiority of zongertinib (BI 1810631) over SoC in terms of the difference in objective response (OR), to show superiority of zongertinib (BI 1810631) over SoC based on the change from baseline at Week 25 in the NSCLC SAQ total score, and to show superiority of zongertinib (BI 1810631) over SoC based on the hazard ratio of OS. The key secondary endpoints are OR per RECIST 1.1 determined by central independent review, the change from baseline at Week 25 in the NSCLC-SAQ total score, and OS.
2. Secondary objectives are to evaluate additional efficacy parameters, further patient reported outcomes (PROs), and safety of zongertinib (BI 1810631) compared with SoC.

Conditions and MedDRA coding

non-squamous non-small cell lung cancer

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Signed and dated written informed consent form (ICF) in accordance with ICH-GCP and local legislation prior to admission to the trial.
2. 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.
3. Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous NSCLC.
4. Documented HER2 mutation in the TKD as per local lab results.
5. An archival tumor tissue sample must be submitted to the central laboratory after inclusion of the patient to retrospectively confirm the HER2 status. If no archival tissue is available, this may be acceptable in exceptional cases after written agreement with the sponsor.
6. Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease and are not eligible for curative therapy.
7. Presence of at least one measurable non-CNS lesion according to RECIST 1.1, as determined by the local site investigator/radiology assessment.
8. "Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the SmPC/Product Information."
9. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 [R01-0787].
10. Adequate organ function as defined in the protocol.
11. Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator.
12. "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 dual highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly."

Exclusion criteria 11

1. "Previous or concomitant malignancies other than the one treated in this trial within the last 5 years, except; i. effectively treated non-melanoma skin cancers ii. effectively treated carcinoma in situ of the cervix iii. effectively treated ductal carcinoma in situ iv. other effectively treated malignancy that is considered cured by local treatment"
2. Tumors with targetable alterations with approved available therapy.
3. Lung-specific intercurrent clinically significant severe illness based on investigators assessment.
4. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
5. Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening, e.g. hip replacement.
6. "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."
7. "History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ≥ III or IV, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator. Myocardial infarction, stroke, or pulmonary embolism within 6 months prior to randomization."
8. 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.
9. Mean resting corrected QT interval (QTcF) >470 msec.
10. "Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval."
11. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is PFS according to RECIST 1.1 determined by blinded central independent review.

Secondary endpoints 8

1. The key secondary endpoints are OR according to RECIST 1.1, determined by blinded central independent review, the change from baseline to Week 25 of NSCLC-SAQ total score, and OS.
2. Duration of response (DoR), determined by blinded central independent review.
3. Progression free survival, determined by blinded central independent review.
4. Bi-compartmental PFS, determined by blinded central independent review.
5. Overall response, determined by blinded central independent review.
6. Further patient reported outcomes (PROs) from NSCLC-SAQ and EORTC QLQ-C30 domain scores, analyzed as change from baseline to Week 25
7. Occurrence of AEs during the on-treatment period, graded according to CTCAE version 5.0.
8. Occurrence of serious AEs (SAEs) during the on-treatment period, graded according to CTCAE version 5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 1

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

Postcode

08174

Country

Spain

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

13 EU/EEA countries · 63 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 410 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications