First in Human Study of BAY2927088 in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations in the Genes of Epidermal Growth Factor Receptor (EGFR) and/or Human Epidermal Growth Factor Receptor 2 (HER2)
NCT ID: NCT05099172
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
370 participants
INTERVENTIONAL
2021-10-25
2026-12-31
Brief Summary
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Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are proteins that help cells to grow and divide. A damage (also called mutation) to the building plans (genes) for these proteins in cancer cells leads to a production of abnormal EGFR and/or HER2. These abnormal proteins drive the growth and the spread of the cancer. Several EGFR and/or HER2 mutations exist in the cancer cells. The study treatment, BAY2927088, is expected to block the mutated EGFR and HER2 proteins which may stop the spread of NSCLC.
The main purpose of this study is to learn:
Escalation, Backfill, and Expansion Part:
* How safe is BAY2927088 for the participants?
* What is the highest dose of BAY2927088 that can be tolerated (maximum tolerated dose) by or given to (maximum administered dose) the participants?
* How does BAY2927088 move into, through, and out of the bodies of the participants?
For this, the researchers will measure the followings:
* The number of participants with medical problems, also called adverse events and serious adverse events, and their severity
* The number of participants who discontinue study treatment due to an adverse event.
* The highest dose of BAY2927088 that the participants can take without having adverse events (maximum tolerated dose (MTD)) or the maximum dose that is tested and found to be safe for the participants in case MTD cannot be found out (maximum administered dose (MAD)) of BAY2927088
* Number of participants experiencing adverse events that prevent an increase in the dose of BAY2927088 (dose-limiting toxicities (DLTs)) at each dose level
* The (average) total level of BAY2927088 in the blood (also called AUC) after receiving single or multiple doses of BAY2927088
* The (average) highest level of BAY2927088 in the blood (also called Cmax) after receiving a single or multiple doses of BAY2927088 Extension Part
* How well does BAY2927088 work in participants?
For this, the researchers will measure the following:
• Percentage of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)). This will be assessed by doctors other than the study doctor.
This study has 4 parts:
* The escalation part aims to find the maximum daily amount (dose) of BAY2927088 that participants can receive.
* The backfill part aims to test the doses of BAY2927088 that are considered safe in the escalation part by giving it to more participants. This will help find optimal doses of BAY2927088 that work well and are safe to be tested in the next part.
* The expansion part aims to determine the dose of BAY2927088 to be tested in further studies.
* The extension part aims to determine whether the selected dose of BAY2927088 from the expansion part works well.
The participants in this study will take the study treatment BAY2927088 in 3-week periods called "cycles". They will in general take BAY2927088 once or twice daily as a liquid/tablet by mouth until their cancer gets worse, they have medical problems, they leave the study, or the study is terminated. Participants will have no more than 5 visits per cycle.
During the study, the study team will:
* take blood and urine samples,
* check the status of the cancer by doing computed tomography (CT) or magnetic resonance imaging (MRI) scans,
* check the participants' overall health and heart health,
* ask the participants questions about how they are feeling and what adverse events they are having.
An adverse event is considered "serious" when it leads to death, puts the participant's life at risk, requires hospitalization, causes disability, causes a baby being born with medical problems, or is medically important.
Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Dose escalation
Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD.
BAY2927088_formulation A
Oral administration
BAY2927088_formulation B_1
Oral administration
BAY2927088_formulation B_2
Oral administration
Backfill
Dose Escalation and Backfill run concurrently
BAY2927088_formulation A
Oral administration
BAY2927088_formulation B_1
Oral administration
BAY2927088_formulation B_2
Oral administration
Dose expansion
Eight independent groups (group A, B1, B2, C, D, E, F, G) are planned. Dose Expansion may start at a dose level that has been evaluated in Escalation/Backfill in at least 9 participants and considered safe or at any other dose levels that are below the highest dose level that is considered safe.
BAY2927088_formulation B_1
Oral administration
BAY2927088_formulation B_2
Oral administration
Extension part
Initiation of the Extension part will depend on the benefit-risk profile observed during Dose Expansion. Additionally, enrollment may be prematurely terminated based on emerging data at the discretion of the Sponsor.
BAY2927088_formulation B_1
Oral administration
BAY2927088_formulation B_2
Oral administration
Interventions
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BAY2927088_formulation A
Oral administration
BAY2927088_formulation B_1
Oral administration
BAY2927088_formulation B_2
Oral administration
Eligibility Criteria
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Inclusion Criteria
* Documented disease progression after treatment with at least one prior systemic therapy for advanced disease. Participants who do not have standard of care access due to any reason, are intolerant to, or are not eligible for standard treatments, may also be eligible.
Note: Except for participants eligible for one of the groups (Expansion or Extension) who should have received no prior systemic treatment for locally advanced or metastatic disease.
* Adequate archival tumor tissue (ideally taken after last targeted treatment and not older than 6 months) has to be available, either from primary or metastatic sites. If archival material is not available, a fresh tumor biopsy should be performed if feasible and if the procedure poses no significant risk for the participant.
* Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy during the screening period (if a biopsy is taken during screening) that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied lesion should not be used as a target lesion for RECIST 1.1 tumor assessments (or, for participants in Expansion Group G, for RANO-BM tumor assessments). Previously irradiated lesions must have shown progression to be considered measurable.
* Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (United States \[US\] sites) or an equally accredited (outside of the US) local laboratory
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Minimum life expectancy of 12 weeks.
* Adequate bone marrow function as assessed by the following laboratory tests to be conducted within 7 days before the first dose of study treatment:
1. Hemoglobin ≥ 9.0 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.
2. Platelets ≥ 100 × 10\^9 cells/L.
3. Absolute neutrophil count ≥ 1.5 ×10\^9 cells/L. Criteria must be met without the use of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to testing.
* Adequate kidney function as assessed by following laboratory test to be conducted within 7 days before the first dose of study treatment:
a. Estimated glomerular filtration rate (eGFR) \> 50 mL/min per 1.73 m\^2 according to the Modification of Diet in renal Disease Study Group (MDRD) formula.
* Adequate liver function as assessed by following laboratory tests to be conducted within 7 days before the first dose of study treatment:
1. Total bilirubin ≤ 1.5 × ULN (or ≤ 3 X ULN for participants with documented Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia considered due to liver metastasis).
2. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN (or ≤ 5 × ULN if due to liver involvement by tumor).
Exclusion Criteria
* Treatment with a systemic anti-cancer treatment (excluding EGFR TKIs as described above) ≤ 14 days prior to the first dose of study drug.
* Radiation therapy, stereotactic radiosurgery (SRS) and palliative radiation ≤ 14 days prior to the first dose of study drug.
* Treatment with immunotherapy ≤ 28 days prior to the first dose of study drug.
* Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
* Any history of primary brain or leptomeningeal disease (symptomatic or asymptomatic), presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local treatment (such as radiotherapy or surgery).
* History of spinal cord compression or brain metastases with the following exceptions:
1. Participants with treated brain metastases that are asymptomatic at screening and who are off or receiving low-dose corticosteroids (≤10 mg prednisone or equivalent) for at least 7 days prior to first dose of BAY 2927088 are eligible to enroll in Dose Escalation and Backfill.
2. Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion/Extension (with the exception of Group G) if all of the following criteria are met:
* there is no evidence of progression (new or enlarging brain metastases) for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
* Participants must be off or receiving low-dose corticosteroids (≤10 mg prednisone or equivalent) for 7 days prior to first dose of BAY2927088.
3. Participants with history of spinal cord compression \>3 months from definitive therapy and stable by imaging (MRI or CT) during the screening period and clinically asymptomatic.
4. Expansion Group G only: Participants with active (new or progressing) clinically stable brain metastases who do not require immediate CNS-directed treatment as per Investigator's judgement and who are off or receiving low-dose corticosteroids (≤10 mg prednisone or equivalent such as ≤ 1.5 mg/day dexamethasone) in the 7 days prior to first dose of BAY2927088 are eligible.
* History of congestive heart failure (CHF) Class \>II according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment (e.g. ventricular arrhythmias, atrial fibrillation) or any clinically important abnormalities in rhythm, conduction or morphology or resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250 msec)
* Participants with:
1. Known human immunodeficiency virus (HIV), except as noted below: Participants with history of HIV infection are eligible at the Investigator's discretion provided that: • CD4+ T-cell (CD4+) counts are ≥ 350 cells/uL • The participant has been on established antiretroviral therapy (ART) for at least 4 weeks prior to the start of study drug and has an HIV viral load less than 400 copies/mL prior to start of the study treatment • The ART being used does not contain strong inducers or inhibitors of CYP3A4, and is not anticipated to cause overlapping toxicities with study drug • The participant has not had an opportunistic infection within the past 12 months
2. Active Hepatitis B infection (positive for Hepatitis B surface antigen \[HbsAg\]) and Hepatitis B virus \[HBV\] DNA).
3. Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA results greater than the lower limits of detection of the assay).
NOTE: Participants with history of chronic HBV or HCV infection are eligible at the Investigator's discretion provided that the disease is stable and sufficiently controlled under treatment.
* Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first administration of study drug. Strong CYP3A4 inhibitors and inducers are prohibited during the study and until Safety FU (follow up) visit.
18 Years
ALL
No
Sponsors
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Bayer
INDUSTRY
Responsible Party
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Locations
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Banner MD Anderson Cancer Center at Banner Gateway Medical Center
Gilbert, Arizona, United States
City of Hope - Duarte Cancer Center
Duarte, California, United States
Emory Winship Cancer Institute
Atlanta, Georgia, United States
The Center for Cancer and Blood Disorders
Bethesda, Maryland, United States
Dana-Farber Cancer Institute - Oncology Department
Boston, Massachusetts, United States
Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit
Detroit, Michigan, United States
NYU Langone Hospital - Long Island - Urology
Mineola, New York, United States
Tennessee Oncology - Nashville Centennial Clinic
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center - Texas Medical Center
Houston, Texas, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, United States
UZ Leuven Gasthuisberg - Pneumology Department
Leuven, Vlaams-Brabant, Belgium
AZ Delta | Clinical Trial Center - Pneumology
Roeselare, West-Flanders, Belgium
Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica
Natal, Rio Grande do Norte, Brazil
Hospital de Base | Integrated Research Center
São José do Rio Preto, São Paulo, Brazil
Beijing Cancer Hospital - Oncology Department
Beijing, Beijing Municipality, China
Beijing Hospital
Beijing, Beijing Municipality, China
Fujian Cancer Hospital
Fuzhou, Fujian, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
Union Hospi, Tongji Med College, Huazhong Univ. Scien&Tech
Wuhan, Hubei, China
Hunan Cancer Hospital - Oncology Department
Changsha, Hunan, China
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
Nanjing, Jiangsu, China
Qilu Hosp., Shandong Univ.
Jinan, Shandong, China
Shandong University - Shandong Cancer Hospital
Jinan, Shandong, China
Shanghai Chest Hospital, Shanghai Jiaotong University
Shanghai, Shanghai Municipality, China
West China Hospital Sichuan University
Chengdu, Sichuan, China
Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department
Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
Zhejiang University School of Medicine - Taizhou Hospital of Zhejiang Province
Taizhou, Zhejiang, China
Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale
Bordeaux, , France
UNICANCER - Centre Leon-Berard (CLB) - Medical oncology
Lyon, , France
Hopital Nord Laennec - Oncologie medicale thoracique et digestive
Nantes, , France
Institut Curie - Paris - Oncologie medicale
Paris, , France
Institut de Cancerologie Ouest - Saint Herblain - Oncologie medicale
Saint-Herblain, , France
Gustave Roussy - Departement Oncologie-Radiotherapie
Villejuif, , France
Prince of Wales Hospital
Hong Kong, , Hong Kong
Queen Mary Hospital
Hong Kong, , Hong Kong
Rabin Medical Center | Beilinson Hospital - Internal Medicine C Department
Petah Tikva, , Israel
Chaim Sheba Medical Center
Ramat Gan, , Israel
Azienda Ospedaliero Universitaria Parma - SC Oncologia Medica
Parma, Emilia-Romagna, Italy
Centro di Riferimento Oncologico di Aviano - Oncologia Medica e dei Tumori Immuno-Correlati
Aviano, Friuli Venezia Giulia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I
Rome, Lazio, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1
Milan, Lombardy, Italy
Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative
Milan, Lombardy, Italy
Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia
Rozzano, Lombardy, Italy
Azienda Ospedaliero-Universitaria San Luigi Gonzaga - Oncologia Medica
Orbassano, Piedmont, Italy
Centro Ricerche Cliniche Di Verona S.r.l. - Oncologia
Verona, , Italy
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, Japan
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, Japan
Kanagawa Cancer Center
Yokohama, Kanagawa, Japan
Osaka International Cancer Institute
Osaka, Osaka, Japan
Kindai University Hospital
Sayama, Osaka, Japan
Shizuoka Cancer Center
Sunto, Shizuoka, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan
Tottori University Hospital
Yonago, Tottori, Japan
Okayama University Hospital
Okayama, , Japan
Nederlands Kanker Instituut
Amsterdam, , Netherlands
Erasmus University Medical Center | Research Department - Lung Diseases
Rotterdam, , Netherlands
IPO Porto
Porto, , Portugal
National University Hospital Medical Centre
Singapore, , Singapore
National Cancer Center Singapore - Oncology Department
Singapore, , Singapore
Curie Oncology | Mount Elizabeth Novena
Singapore, , Singapore
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggido, South Korea
St.Vincent's Hospital
Suwon, Gyeonggido, South Korea
Chungbuk National University Hospital
Cheongju-si, North Chungcheong, South Korea
Severance Hospital, Yonsei University Health System - Oncology Department
Seoul, Seoul Teugbyeolsi, South Korea
Asan Medical Center-Ophthalmology
Seoul, Seoul Teugbyeolsi, South Korea
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, South Korea
Samsung Medical Center - Oncology Department
Seoul, , South Korea
Institut Catala D'oncologia - Oncologia
Barcelona, L Hospitalet de Llobregat, Spain
Hospital Quiron Dexeus - Oncologia
Barcelona, , Spain
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
Barcelona, , Spain
Hospital Universitario Fundacion Jimenez Diaz- Oncology Service
Madrid, , Spain
Centro Integral Oncológico Clara Campal
Madrid, , Spain
Hospital Universitario Y Politecnico La Fe - Oncologia
Valencia, , Spain
Taichung Veterans General Hospital
Taichung, , Taiwan
National Cheng Kung University Hospital
Tainan, , Taiwan
Chi-Mei Medical Center, Liouyine
Tainan, , Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
Chang Gung Memorial Hospital at Linkou
Taoyuan District, , Taiwan
Countries
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References
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Le X, Kim TM, Loong HH, Prelaj A, Goh BC, Li L, Fang Y, Lu S, Dong X, Wu L, Shinno Y, Daniele G, Yang TY, Kim HR, Ruiter G, Zhao J, Novello S, Miao L, Janne PA, Goto K, Ruttinger D, Descamps T, Brase JC, Bao W, Li R, Brega N, Grassi P, Girard N, Tan DS; SOHO-01 Investigators. Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2025 Oct 17. doi: 10.1056/NEJMoa2511065. Online ahead of print.
Related Links
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Other Identifiers
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2023-503795-24-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
2021-003022-77
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
21607
Identifier Type: -
Identifier Source: org_study_id