Sponsor: Boehringer Ingelheim (industry)
Phase: 3
Start date: Feb. 9, 2024
Planned enrollment: 270
Last updated in HealthScout: Nov 2024
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.
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)
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)
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)
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)
Last updated: Apr 2025
Last updated: Apr 2025
Goal: The goal of the Beamion LUNG 2 trial is to evaluate the efficacy and safety of the orally administered investigational drug zongertinib (BI 1810631) compared to the current standard of care treatment, pembrolizumab combined with platinum-pemetrexed chemotherapy, as a first-line treatment for patients with advanced non-squamous non-small cell lung cancer harboring HER2 tyrosine kinase domain mutations.
Patients: The trial targets adults aged 18 and older diagnosed with unresectable, locally advanced or metastatic non-small cell lung cancer possessing HER2 mutations. These patients must not have received any prior systemic therapy for their advanced condition and must possess at least one measurable lesion according to RECIST 1.1 guidelines.
Design: This is a Phase III, open-label, randomized, active-controlled, multi-centre clinical trial. Participants are randomly assigned to either the experimental group receiving zongertinib or the comparator group receiving the standard chemotherapy regimen.
Treatments: The investigational treatment, zongertinib (BI 1810631), is a novel tyrosine kinase inhibitor specifically targeting HER2 mutations in NSCLC while avoiding EGFR-associated toxicities, leading to a manageable safety profile. Phase Ia/Ib results demonstrated an objective response rate up to 74% and a disease control rate of 91%. The standard treatment involves pembrolizumab combined with platinum-pemetrexed chemotherapy, an established regimen for treating metastatic non-small cell lung cancer.
Outcomes: The primary outcome is progression-free survival as per RECIST 1.1. Secondary outcomes include overall response, change in NSCLC-SAQ scores, overall survival, duration of response, occurrence of adverse events, and quality of life measures. These outcomes will assess the efficacy, safety, and patient quality of life associated with the treatments.
Burden on patient: The participant burden is assessed as moderate. Patients are required to have regular follow-up visits every three weeks, involving CT or MRI scans every six weeks initially, and every twelve weeks after eighteen months. The burden is lower than in early-phase trials due to the oral administration of zongertinib and routine standard of care procedures, minimizing extensive invasive testing or pharmacokinetic blood draws.
Inclusion criteria:
1. Signed and dated written informed consent form (ICF) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (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 Non-small cell lung cancer (NSCLC).
4. Documented Human epidermal growth factor receptor 2 (HER2) mutation in the Tyrosine kinase domain (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 lesion according to Response evaluation criteria in solid tumors (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 Summaries of Product Characteristics (SmPC)/Product Information.
Further inclusion criteria apply.
Exclusion criteria:
1. Previous or concomitant malignancies other than the one treated in this trial within the last 5 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
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 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, 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.
Further exclusion criteria apply.
La Rioja, F5300COE, Argentina
[email protected] / 08002667801
Status: Not yet recruiting
Viedma, R8500ACE, Argentina
[email protected] / 08002667801
Status: Not yet recruiting
Rosario, S2000DEJ, Argentina
[email protected] / 08002667801
Status: Not yet recruiting
Caba, 1430, Argentina
[email protected] / 08002667801
Status: Not yet recruiting
Ciudad Autónoma de Bs As, C1426ANZ, Argentina
[email protected] / 08002667801
Status: Not yet recruiting
Córdoba, X5000, Argentina
[email protected] / 08002667801
Status: Not yet recruiting
St Leonards, New South Wales, 2065, Australia
[email protected] / 1800271035
Status: Recruiting
Randwick, New South Wales, 2031, Australia
[email protected] / 1800271035
Status: Not yet recruiting
Woolloongabba, Queensland, 4102, Australia
[email protected] / 1800271035
Status: Recruiting
Heidelberg, Victoria, 3084, Australia
[email protected] / 1800271035
Status: Recruiting
Subiaco, Western Australia, 6008, Australia
[email protected] / 1800271035
Status: Recruiting
Vienna, 1210, Austria
[email protected] / 0800017900
Status: Recruiting
Krems an der Donau, 3500, Austria
[email protected] / 0800017900
Status: Recruiting
Gent, 9000, Belgium
[email protected] / 080049616
Status: Recruiting
Anderlecht, 1070, Belgium
[email protected] / 080049616
Status: Recruiting
Leuven, 3000, Belgium
[email protected] / 080049616
Status: Recruiting
Rio de Janeiro, 22250-040, Brazil
[email protected] / 08008919295
Status: Not yet recruiting
Londrina, 86015-520, Brazil
[email protected] / 08008919295
Status: Not yet recruiting
Bento Goncalves, 95700-084, Brazil
[email protected] / 08008919295
Status: Not yet recruiting
Porto Alegre, 90610-000, Brazil
[email protected] / 08008919295
Status: Recruiting
São José do Rio Preto, 15090-000, Brazil
[email protected] / 08008919295
Status: Not yet recruiting
Sao Paulo, 01246-000, Brazil
[email protected] / 08008919295
Status: Recruiting
Santo André, 09060-650, Brazil
[email protected] / 08008919295
Status: Not yet recruiting
Recoleta, 8420383, Chile
[email protected] / 800392345
Status: Recruiting
Xiamen, 361003, China
[email protected] / 4001200553
Status: Not yet recruiting
Beijing, 1000021, China
[email protected] / 4001200553
Status: Not yet recruiting
Beijing, 100142, China
[email protected] / 4001200553
Status: Recruiting
Chengdu, 610042, China
[email protected] / 4001200553
Status: Recruiting
Fuzhou, 350014, China
[email protected] / 4001200553
Status: Recruiting
Guangzhou, 510080, China
[email protected] / 4001200553
Status: Recruiting
Hangzhou, 310003, China
[email protected] / 4001200553
Status: Recruiting
Hangzhou, 310016, China
[email protected] / 4001200553
Status: Not yet recruiting
Hangzhou, 310022, China
[email protected] / 4001200553
Status: Recruiting
Harbin, 150081, China
[email protected] / 4001200553
Status: Recruiting
Shanghai, 200032, China
[email protected] / 4001200553
Status: Recruiting
Shanghai, 200032, China
[email protected] / 4001200553
Status: Recruiting
Taizhou, 317099, China
[email protected] / 4001200553
Status: Recruiting
Tianjin, 300060, China
[email protected] / 4001200553
Status: Recruiting
Wenzhou, 325000, China
[email protected] / 4001200553
Status: Recruiting
Wuhan, 430022, China
[email protected] / 4001200553
Status: Recruiting
Zhengzhou, 450008, China
[email protected] / 4001200553
Status: Recruiting
Rennes, 35000, France
[email protected] / 0805102354
Status: Recruiting
Villejuif, 94805, France
[email protected] / 0805102354
Status: Recruiting
Toulouse, 31059, France
[email protected] / 0805102354
Status: Recruiting
Strasbourg, 67091, France
[email protected] / 0805102354
Status: Recruiting
Bron, 69677, France
[email protected] / 0805102354
Status: Not yet recruiting
Lyon, 69373, France
[email protected] / 0805102354
Status: Recruiting
Marseille, 13015, France
[email protected] / 0805102354
Status: Recruiting
Paris, 75020, France
[email protected] / 0805102354
Status: Recruiting
Paris, 75248, France
[email protected] / 0805102354
Status: Recruiting
Oldenburg, 26121, Germany
[email protected] / 08007234742
Status: Recruiting
Heidelberg, 69126, Germany
[email protected] / 08007234742
Status: Recruiting
Köln, 50937, Germany
[email protected] / 08007234742
Status: Recruiting
Tübingen, 72076, Germany
[email protected] / 08007234742
Status: Not yet recruiting
Augsburg, 86156, Germany
[email protected] / 08007234742
Status: Not yet recruiting
Berlin, 14089, Germany
[email protected] / 08007234742
Status: Recruiting
Dresden, 01307, Germany
[email protected] / 08007234742
Status: Recruiting
Gießen, 35392, Germany
[email protected] / 08007234742
Status: Not yet recruiting
Hong Kong, 999077, Hong Kong
[email protected] / 800965365
Status: Not yet recruiting
Hong Kong, 999077, Hong Kong
[email protected] / 800965365
Status: Recruiting
Hong Kong, 51727, Hong Kong
[email protected] / 800965365
Status: Recruiting
Deszk, 6772, Hungary
[email protected] / 680017725
Status: Not yet recruiting
Budapest, 1122, Hungary
[email protected] / 680017725
Status: Not yet recruiting
Budapest, 1122, Hungary
[email protected] / 680017725
Status: Not yet recruiting
Farkasgyepu, 8582, Hungary
[email protected] / 680017725
Status: Not yet recruiting
Szekesfehervar, 8000, Hungary
[email protected] / 680017725
Status: Not yet recruiting
Haifa, 3109601, Israel
[email protected] / 1809388162
Status: Recruiting
Tel Aviv, 6423906, Israel
[email protected] / 1809388162
Status: Recruiting
Petach Tikva, 49100, Israel
[email protected] / 1809388162
Status: Not yet recruiting
Kfar-Saba, 4428164, Israel
[email protected] / 1809388162
Status: Recruiting
Napoli, 80131, Italy
[email protected] / 800977373
Status: Recruiting
Catania, 95123, Italy
[email protected] / 800977373
Status: Recruiting
Candiolo (TO), 10060, Italy
[email protected] / 800977373
Status: Not yet recruiting
Bari, 70124, Italy
[email protected] / 800977373
Status: Not yet recruiting
Varese, 21100, Italy
[email protected] / 800977373
Status: Not yet recruiting
Roma, 00161, Italy
[email protected] / 800977373
Status: Not yet recruiting
Parma, 43100, Italy
[email protected] / 800977373
Status: Not yet recruiting
Kyoto, Kyoto, 602-8566, Japan
[email protected] / 0120201230
Status: Recruiting
Aichi, Nagoya, 464-8681, Japan
[email protected] / 0120201230
Status: Not yet recruiting
Aomori, Hirosaki, 036-8563, Japan
[email protected] / 0120201230
Status: Recruiting
Chiba, Kashiwa, 277-8577, Japan
[email protected] / 0120201230
Status: Not yet recruiting
Ehime, Matsuyama, 791-0280, Japan
[email protected] / 0120201230
Status: Recruiting
Fukuoka, Fukuoka, 812-8582, Japan
[email protected] / 0120201230
Status: Recruiting
Hokkaido, Hakodate, 040-8611, Japan
[email protected] / 0120201230
Status: Recruiting
Hokkaido, Sapporo, 003-0804, Japan
[email protected] / 0120201230
Status: Recruiting
Ishikawa, Kanazawa, 920-8641, Japan
[email protected] / 0120201230
Status: Not yet recruiting
Kanagawa, Kawasaki, 216-8511, Japan
[email protected] / 0120201230
Status: Recruiting
Kanagawa, Yokohama, 241-8515, Japan
[email protected] / 0120201230
Status: Recruiting
Miyagi, Sendai, 980-8574, Japan
[email protected] / 0120201230
Status: Recruiting
Okayama, Okayama, 700-8558, Japan
[email protected] / 0120201230
Status: Recruiting
Osaka, Osaka, 541-8567, Japan
[email protected] / 0120201230
Status: Not yet recruiting
Shizuoka, Sunto-gun, 411-8777, Japan
[email protected] / 0120201230
Status: Recruiting
Tokyo, Bunkyo-ku, 113-8431, Japan
[email protected] / 0120201230
Status: Recruiting
Tokyo, Bunkyo-ku, 113-8677, Japan
[email protected] / 0120201230
Status: Recruiting
Tokyo, Chuo-ku, 104-0045, Japan
[email protected] / 0120201230
Status: Recruiting
Tokyo, Koto-ku, 135-8550, Japan
[email protected] / 0120201230
Status: Recruiting
Wakayama, Wakayama, 641-8510, Japan
[email protected] / 0120201230
Status: Recruiting
Suwon, 16247, Korea, Republic of
[email protected] / 0808802084
Status: Recruiting
Incheon, 21565, Korea, Republic of
[email protected] / 0808802084
Status: Not yet recruiting
Seoul, 03181, Korea, Republic of
[email protected] / 0808802084
Status: Recruiting
Seoul, 03722, Korea, Republic of
[email protected] / 0808802084
Status: Recruiting
Cheongiu, 28644, Korea, Republic of
[email protected] / 0808802084
Status: Recruiting
Seoul, 05505, Korea, Republic of
[email protected] / 0808802084
Status: Recruiting
Goyang, 10408, Korea, Republic of
[email protected] / 0808802084
Status: Recruiting
Seoul, 06351, Korea, Republic of
[email protected] / 0808802084
Status: Recruiting
Mexico, 14080, Mexico
[email protected] / 018000623749
Status: Not yet recruiting
Ciudad de Mexico, 03100, Mexico
[email protected] / 018000623749
Status: Recruiting
Veracruz, 91900, Mexico
[email protected] / 018000623749
Status: Not yet recruiting
Mexico, 06760, Mexico
[email protected] / 018000623749
Status: Recruiting
Maastricht, 6229 HX, Netherlands
[email protected] / 08000204613
Status: Recruiting
Amsterdam, 1066 CX, Netherlands
[email protected] / 08000204613
Status: Recruiting
Oslo, 0379, Norway
[email protected] / 80058261
Status: Not yet recruiting
Drammen, N-3004, Norway
[email protected] / 80058261
Status: Not yet recruiting
Poznan, 60693, Poland
[email protected] / 008001218830
Status: Not yet recruiting
Lodz, 93-338, Poland
[email protected] / 008001218830
Status: Not yet recruiting
Poznan, 60-569, Poland
[email protected] / 008001218830
Status: Not yet recruiting
Warsaw, 02-781, Poland
[email protected] / 008001218830
Status: Not yet recruiting
Porto, 4100-180, Portugal
[email protected] / 800856070
Status: Recruiting
Lisboa, 1350-352, Portugal
[email protected] / 800856070
Status: Not yet recruiting
Lisboa, 1769-001, Portugal
[email protected] / 800856070
Status: Not yet recruiting
Rio Piedras, 00935, Puerto Rico
[email protected] / 18336022368
Status: Not yet recruiting
Singapore, 119228, Singapore
[email protected] / 8001207344
Status: Recruiting
Singapore, 168583, Singapore
[email protected] / 8001207344
Status: Recruiting
A Coruña, 15006, Spain
[email protected] / 900876092
Status: Not yet recruiting
Alicante, 03010, Spain
[email protected] / 900876092
Status: Not yet recruiting
Barcelona, 08026, Spain
[email protected] / 900876092
Status: Not yet recruiting
Barcelona, 08035, Spain
[email protected] / 900876092
Status: Recruiting
Bilbao, 48013, Spain
[email protected] / 900876092
Status: Recruiting
L'Hospitalet de Llobregat, 08908, Spain
[email protected] / 900876092
Status: Recruiting
Madrid, 28009, Spain
[email protected] / 900876092
Status: Not yet recruiting
Madrid, 28034, Spain
[email protected] / 900876092
Status: Recruiting
Madrid, 28041, Spain
[email protected] / 900876092
Status: Recruiting
Madrid, 28046, Spain
[email protected] / 900876092
Status: Not yet recruiting
Málaga, 29010, Spain
[email protected] / 900876092
Status: Not yet recruiting
Sevilla, 41013, Spain
[email protected] / 900876092
Status: Recruiting
Valencia, 46010, Spain
[email protected] / 900876092
Status: Recruiting
Göteborg, 413 45, Sweden
[email protected] / 0200880001
Status: Not yet recruiting
Stockholm, 171 76, Sweden
[email protected] / 0200880001
Status: Not yet recruiting
Taoyuan, 330, Taiwan
[email protected] / 0809092098
Status: Recruiting
Taichung, 404, Taiwan
[email protected] / 0809092098
Status: Recruiting
Kaohsiung, 83301, Taiwan
[email protected] / 0809092098
Status: Not yet recruiting
Taipei, 100, Taiwan
[email protected] / 0809092098
Status: Not yet recruiting
Taipei, 106, Taiwan
[email protected] / 0809092098
Status: Recruiting
London, SW3 6JJ, United Kingdom
[email protected] / 08000514022
Status: Recruiting
Leicester, LE1 5WW, United Kingdom
[email protected] / 08000514022
Status: Not yet recruiting
London, SE1 9RT, United Kingdom
[email protected] / 08000514022
Status: Recruiting
Edinburgh, EH4 2XU, United Kingdom
[email protected] / 08000514022
Status: Not yet recruiting
Sutton, SM2 5PT, United Kingdom
[email protected] / 08000514022
Status: Recruiting
Huntsville, Alabama, 35805, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Bullhead City, Arizona, 86442, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
La Jolla, California, 92037, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Fresno, California, 93710, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Beverly Hills, California, 90212, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Los Angeles, California, 90067, United States
[email protected] / 833-602-2368
Status: Recruiting
Glendale, California, 91203, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Bridgeton, Missouri, 63044, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Springfield, Missouri, 65807, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Reno, Nevada, 89511, United States
[email protected] / 833-602-2368
Status: Recruiting
Lake Success, New York, 11042, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Bronx, New York, 10461, United States
[email protected] / 833-602-2368
Status: Recruiting
Wilson, North Carolina, 27893, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Canton, Ohio, 44718, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Rock Hill, South Carolina, 29732, United States
No email / No phone
Status: Completed
Nashville, Tennessee, 37203, United States
[email protected] / 833-602-2368
Status: Recruiting
Salt Lake City, Utah, 84112, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Fairfax, Virginia, 22031, United States
[email protected] / 833-602-2368
Status: Recruiting
Seattle, Washington, 98104, United States
[email protected] / 833-602-2368
Status: Recruiting
Issaquah, Washington, 98029, United States
[email protected] / 833-602-2368
Status: Not yet recruiting
Edmonds, Washington, 98026, United States
[email protected] / 833-602-2368
Status: Not yet recruiting