Advanced Non-small Cell Lung CancerPhase 1/2NCT05099172
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)
A Phase 1/2 study testing BAY2927088_formulation A, BAY2927088_formulation B_1 and BAY2927088_formulation B_2 in people with Advanced Non-small Cell Lung Cancer and EGFR Mutation, run by Bayer at 94 sites in 16 countries.
Trial summary
Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other parts of the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Non-small Cell Lung Cancer, EGFR Mutation, HER2 Mutation
- What is being tested?
- BAY2927088_formulation A, BAY2927088_formulation B_1 and BAY2927088_formulation B_2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 430 participants
- Where
- 94 sitesin 16 countries
- Study dates
- 25 Oct 2021to 30 Jun 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented histologically or cytologically confirmed locally advanced NSCLC, not suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small cell or mixed histologies are excluded).
- 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 Group F, Group H and Group I (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 (or by RANO-BM for participants in Expansion Groups G and H) with at least one lesion that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements.
- 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.
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- 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:
- 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.
- Platelets ≥ 100 × 10^9 cells/L.
- 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:
- 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:
- Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN for participants with documented Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia considered due to liver metastasis).
- Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN (or ≤ 5 × ULN if due to liver involvement by tumor).
Who cannot join
- Treatment with an EGFR tyrosine kinase inhibitor (TKI) ≤ 8 days or 5x the terminal phase, elimination half-lives, whichever is shorter, prior to the first dose of study drug.
- 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).
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- History of spinal cord compression or brain metastases with the following exceptions:
- 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 sevabertinib are eligible to enroll in Dose Escalation and Backfill.
- Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion/Extension (with the exception of Groups G and H) 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 sevabertinib.
- 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.
- Expansion Group G and Group H: 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 sevabertinib 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:
- 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
- Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg]) and Hepatitis B virus [HBV] DNA).
- 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.
Trial locations and contacts
94 sites in 16 countries. Contact the study team or a site near you to ask about taking part.
94 sites in 16 countries
China14 sites
- Active, not recruiting
Beijing Cancer Hospital - Oncology Department
Beijing, Beijing Municipality, 100142
- Active, not recruiting
Beijing Hospital
Beijing, Beijing Municipality, 100730
- Active, not recruiting
Hunan Cancer Hospital - Oncology Department
Changsha, Hunan, 410013
- Active, not recruiting
West China Hospital Sichuan University
Chengdu, Sichuan, 610041
- Active, not recruiting
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
- Active, not recruiting
Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department
Hangzhou, Zhejiang, 310016
- Active, not recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
- Terminated
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000
- Terminated
Qilu Hospital of Shandong University
Jinan, Shandong, 250012
- Active, not recruiting
Shandong University - Shandong Cancer Hospital
Jinan, Shandong, 250117
- Active, not recruiting
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008
- Active, not recruiting
Shanghai Chest Hospital, Shanghai Jiaotong University
Shanghai, Shanghai Municipality, 200030
- Active, not recruiting
Zhejiang University School of Medicine - Taizhou Hospital of Zhejiang Province
Taizhou, Jiangsu, 317000
- Active, not recruiting
Union Hospi, Tongji Med College, Huazhong Univ. Scien&Tech
Wuhan, Hubei, 430023
United States11 sites, 1 recruiting
- Active, not recruiting
Emory Winship Cancer Institute
Atlanta, Georgia, 30322
- Withdrawn
The Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
- Completed
Dana-Farber Cancer Institute - Oncology Department
Boston, Massachusetts, 02215
- Withdrawn
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
- Completed
Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit
Detroit, Michigan, 48202
- Completed
City of Hope - Duarte Cancer Center
Duarte, California, 91010
- Withdrawn
Inova Schar Cancer Insitute - Inova Fairfax Hospital
Fairfax, Washington, 22031
- Completed
Virginia Cancer Specialists, PC - Fairfax
Fairfax, Washington, 22031
- Completed
Banner MD Anderson Cancer Center at Banner Gateway Medical Center
Gilbert, Arizona, 85234
- Active, not recruiting
The University of Texas MD Anderson Cancer Center - Texas Medical Center
Houston, Texas, 77030
- Recruiting
Tennessee Oncology - Nashville Centennial Clinic
Nashville, Tennessee, 37203
Japan11 sites
- Active, not recruiting
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
- Active, not recruiting
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
- Completed
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
- Active, not recruiting
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, 464-8681
- Terminated
Okayama University Hospital
Okayama, 700-8558
- Active, not recruiting
Osaka International Cancer Institute
Osaka, 541-8567
- Active, not recruiting
Kindai University Hospital
Sakai, Osaka, 590-0197
- Active, not recruiting
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
- Completed
Shizuoka Cancer Center
Sunto, Shizuoka, 411-8777
- Active, not recruiting
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
- Completed
Tottori University Hospital
Yonago, Tottori, 683-8504
Italy9 sites
- Active, not recruiting
Centro di Riferimento Oncologico di Aviano - Oncologia Medica e dei Tumori Immuno-Correlati
Aviano, Friuli Venezia Giulia, 33081
- Active, not recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1
Milan, Lombardy, 20133
- Completed
Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative
Milan, Lombardy, 20141
- Withdrawn
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Naples, Campania, 80131
- Active, not recruiting
Azienda Ospedaliero-Universitaria San Luigi Gonzaga - Oncologia Medica
Orbassano, Piedmont, 10043
- Active, not recruiting
Azienda Ospedaliero Universitaria Parma - SC Oncologia Medica
Parma, Emilia-Romagna, 43126
- Active, not recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I
Rome, Lazio, 00128
- Active, not recruiting
Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia
Rozzano, Lombardy, 20089
- Completed
Centro Ricerche Cliniche Di Verona S.r.l. - Oncologia
Verona, Veneto, 37134
France7 sites
- Completed
Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale
Bordeaux, New Aquitaine, 33000
- Active, not recruiting
UNICANCER - Centre Leon-Berard (CLB) - Medical oncology
Lyon, Auvergne-Rhône-Alpes, 69373
- Withdrawn
AP-HM - Hopital de la Timone - Centre d'Essais en Cancerologie
Marseille, Provence-Alpes-Côte d'Azur Region, 13005
- Active, not recruiting
Hopital Nord Laennec - Oncologie medicale thoracique et digestive
Nantes, Pays de la Loire Region, 44093
- Completed
Institut Curie - Paris - Oncologie medicale
Paris, Île-de-France Region, 75248
- Active, not recruiting
Institut de Cancerologie Ouest - Saint Herblain - Oncologie medicale
Saint-Herblain, Pays de la Loire Region, 44800
- Completed
Gustave Roussy - Departement Oncologie-Radiotherapie
Villejuif, Île-de-France Region, 94805
South Korea7 sites
- Active, not recruiting
Chungbuk National University Hospital | Hematology and Oncology
Chungcheongbuk-do, North Chungcheong, 28644
- Active, not recruiting
Seoul National University Hospital | Oncology
Jongno -Gu, Seoul, 03080
- Completed
Seoul National University Bundang Hospital | Hematology and Medical Oncology
Seongnam-si, Gyeonggi-do, 13620
- Active, not recruiting
Severance Hospital | Oncology
Seoul, 03722
- Active, not recruiting
Asan Medical Center | Oncology
Seoul, 05505
- Active, not recruiting
Samsung Medical Center | Oncology
Seoul, 06351
- Active, not recruiting
St Vincent's Hospital | Oncology
Suwon, Gyeonggi-do, 16247
Spain7 sites
- Active, not recruiting
Hospital Universitari Dexeus Grupo Quironsalud | Oncologia
Barcelona, 08028
- Active, not recruiting
Hospital Universitari Vall D Hebron | Oncologia
Barcelona, 08035
- Active, not recruiting
Institut Catala D'oncologia | Hospitalet | Oncologia
L'Hospitalet de Llobregat, Barcelona, 08908
- Active, not recruiting
Hospital Universitario Fundacion Jimenez Diaz | Oncologia
Madrid, 28040
- Completed
Hospital Universitario Hm Sanchinarro | Oncologia
Madrid, 28050
- Withdrawn
Hospital Universitario Virgen De La Victoria | Oncologia
Málaga, 29010
- Active, not recruiting
Hospital Universitario Y Politecnico La Fe | Oncologia
Valencia, 46026
Taiwan7 sites
- Withdrawn
Chung Shan Medical University Hospital
Taichung, 402306
- Active, not recruiting
Taichung Veterans General Hospital
Taichung, 40705
- Active, not recruiting
National Cheng Kung University Hospital
Tainan, 704
- Active, not recruiting
Chi-Mei Medical Center, Liouyine
Tainan, 73657
- Active, not recruiting
National Taiwan University Hospital
Taipei, 100
- Withdrawn
Taipei Medical University (TMU) - Shuang Ho Hospital (SHH)
Taipei, 23561
- Active, not recruiting
Chang Gung Memorial Hospital at Linkou
Taoyuan, 33305
Brazil3 sites
- Active, not recruiting
Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica
Natal, Rio Grande do Norte, 59040-000
- Withdrawn
Hospital de Base | Funfarme - Centro Integrado de Pesquisa - Cardiologia
São José do Rio Preto, São Paulo, 15090-000
- Withdrawn
Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department
São Paulo, 05651-901
Hong Kong3 sites, 1 recruiting
- Active, not recruiting
Prince of Wales Hospital
Hong Kong, Hong Kong SAR, 00000
- Active, not recruiting
Queen Mary Hospital
Hong Kong, Hong Kong SAR, 00000
- Recruiting
Hong Kong United Oncology Centre
Kowloon, 00000
Netherlands3 sites
- Active, not recruiting
Nederlands Kanker Instituut
Amsterdam, North Holland, 1066 CX
- Withdrawn
Radboud University Medical Center | Afdeling Interne Geneeskunde
Nijmegen, Gelderland, 6500 HB
- Completed
Erasmus University Medical Center | Research Department - Lung Diseases
Rotterdam, South Holland, 3015 GD
Portugal3 sites, 1 recruiting
- Withdrawn
START Research Portugal
Lisbon, 1649-028
- Withdrawn
Hospital Santa Maria | Centro de Investigacao Clinica
Lisbon, 1649-035
- Recruiting
IPO Porto
Porto, 4200-072
Singapore3 sites
- Active, not recruiting
National University Hospital Medical Centre
Singapore, 119074
- Active, not recruiting
National Cancer Center Singapore - Oncology Department
Singapore, 168583
- Active, not recruiting
Curie Oncology | Mount Elizabeth Novena
Singapore, 329563
Belgium2 sites
- Active, not recruiting
UZ Leuven Gasthuisberg - Pneumology Department
Leuven, Flemish Brabant, 3000
- Active, not recruiting
AZ Delta | Clinical Trial Center - Pneumology
Roeselare, West Flanders, 8800
Israel2 sites
- Completed
Rabin Medical Center | Beilinson Campus
Petah Tikva, Central District, 4941492
- Completed
Chaim Sheba Medical Center
Ramat Gan, Tel Aviv, 5262000
Poland2 sites
- Withdrawn
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80-214
- Withdrawn
Uniwersytecki Szpital Kliniczny Nr 2 Uniwersytetu Medycznego w Łodzi
Lodz, Łódź Voivodeship, 92-213
About this study
Official title: An Open Label, First-in-human Study of BAY 2927088 in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) Harboring an EGFR and/or HER2 Mutation
Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other parts of the body.
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, sevabertinib (BAY2927088), is expected to block the mutated EGFR and HER2 proteins which may stop the spread of NSCLC.
Read more
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.
- Being tested
- BAY2927088_formulation A, BAY2927088_formulation B_1, BAY2927088_formulation B_2, BAY2927088_formulation B_3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY2927088_formulation ADrug
Oral administration
BAY2927088_formulation B_1Drug
Oral administration
BAY2927088_formulation B_2Drug
Oral administration
BAY2927088_formulation B_3Drug
Oral administration
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD. Receives: Drug: BAY2927088_formulation A; Drug: BAY2927088_formulation B_1; Drug: BAY2927088_formulation B_2 |
| Backfill | Experimental | Dose Escalation and Backfill run concurrently Receives: Drug: BAY2927088_formulation A; Drug: BAY2927088_formulation B_1; Drug: BAY2927088_formulation B_2 |
| Dose expansion | Experimental | Eight independent groups (group A, B1, B2, C, D, E, F, G, H, I, J) 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. Receives: Drug: BAY2927088_formulation B_1; Drug: BAY2927088_formulation B_2; Drug: BAY2927088_formulation B_3 |
| Extension part | Experimental | 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. Receives: Drug: BAY2927088_formulation B_1; Drug: BAY2927088_formulation B_2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-emergent adverse events (TEAEs)
Measured: Up to 30 days after the last administration of study treatment
Number of participants with treatment-emergent serious adverse events (TESAEs)
Measured: Up to 30 days after the last administration of study treatment
Severity of TEAEs
Measured: Up to 30 days after the last administration of study treatment
Severity of TESAEs
Measured: Up to 30 days after the last administration of study treatment
Number of participants who discontinue study treatment due to an AE
Measured: About 4 years (Up to the end of study treatment)
Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2927088 within the DLT observation period in Dose Escalation (including participants from Backfill qualifying for the MTD population)
Measured: At the end of Cycle 1 of a 21-day cycle
Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY2927088 in the DLT observation period in Dose Escalation (including participants from Backfill)
In Dose Escalation (including participants from Backfill)
Measured: At the end of Cycle 1 of a 21-day cycle
Cmax of BAY2927088
Cmax: Maximum/peak concentration
Measured: Cycle 1, Day 1 (Cycle duration is 21 days)
AUC(0-24) of BAY2927088 for QD
AUC: Area under the concentration vs. time curve. AUC(0-24): AUC from time 0 to 24 hours post dose. QD: Quaque die (once daily)
Measured: Cycle 1, Day 1 (Cycle duration is 21 days)
AUC(0-12) of BAY2927088 for BID
If applicable. AUC(0-12): AUC from time 0 to 12 hours post dose. BID: Bis in die, 2 times daily.
Measured: Cycle 1, Day 1 (Cycle duration is 21 days)
Cmax,md of BAY2927088
Cmax,md: Cmax after multiple dose administrations
Measured: Cycle 1, Day 15 (Cycle duration is 21 days)
AUC(0-24)md of BAY2927088 for QD
AUC(0-24)md: AUC(0-24) after multiple dose administrations
Measured: Cycle 1, Day 15 (Cycle duration is 21 days)
AUC(0-12)md of BAY2927088 for BID
If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations
Measured: Cycle 1, Day 15 (Cycle duration is 21 days)
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR) in extension part
Measured: From the start of the study treatment up to 12 months
Secondary outcomes (8)
Overall response rate (ORR) as per RECIST v1.1 by investigator assessment
RECIST v1.1: Response Evaluation Criteria in Solid Tumors, version 1.1
Measured: About 4 years
Recommended phase 2 dose (RP2D) of BAY2927088
Measured: About 1.5 years
ORR per RECIST v1.1 by Investigator assessment in extension part
Measured: From the start of the study treatment up to 12 months
Disease control rate (DCR) per RECIST v1.1 by Investigator assessment and BICR in extension part
Measured: From the start of the study treatment up to 12 months
Duration of response (DOR) per RECIST 1.1 by Investigator assessment and BICR in extension part
Measured: From the start of the study treatment up to 12 months
Progression-free survival (PFS) per RECIST 1.1 by Investigator assessment and BICR in extension part
Measured: From the start of the study treatment up to 12 months
Overall survival (OS) in extension part
Measured: From the start of the study treatment up to 12 months
Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity in extension part
Measured: Up to 30 days after the last administration of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2021
- Study start25 Oct 2021
- Primary completion1 Dec 2028 (estimated)
- Study completion30 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 430 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05099172
- Sponsor's protocol ID
- 21607
- Other IDs
- 2023-503795-24-00, 2021-003022-77, 2023
- Status last verified
- 20 Oct 2026
- First submitted
- 19 Oct 2021
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
- Expanded access
- Available
Publications
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 Nov 6;393(18):1819-1832. doi: 10.1056/NEJMoa2511065. Epub 2025 Oct 17.
PubMed 41104928
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, First-in-human Study of BAY 2927088 in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) Harboring an EGFR and/or HER2 Mutation
- ClinicalTrials.gov ID
- NCT05099172
- Acronym / sponsor ID
- 21607
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 430 participants (estimated)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 25 Oct 2021 (actual)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 30 Jun 2031 (estimated)
- First posted
- 29 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other parts of the body.
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, sevabertinib (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: BAY2927088_formulation A, Drug: BAY2927088_formulation B_1, Drug: BAY2927088_formulation B_2Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD. |
| Backfill | Experimental | Drug: BAY2927088_formulation A, Drug: BAY2927088_formulation B_1, Drug: BAY2927088_formulation B_2Dose Escalation and Backfill run concurrently |
| Dose expansion | Experimental | Drug: BAY2927088_formulation B_1, Drug: BAY2927088_formulation B_2, Drug: BAY2927088_formulation B_3Eight independent groups (group A, B1, B2, C, D, E, F, G, H, I, J) 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. |
| Extension part | Experimental | Drug: BAY2927088_formulation B_1, Drug: BAY2927088_formulation B_2Initiation 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Documented histologically or cytologically confirmed locally advanced NSCLC, not suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small cell or mixed histologies are excluded).
- 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 Group F, Group H and Group I (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 (or by RANO-BM for participants in Expansion Groups G and H) with at least one lesion that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements.
Key exclusion criteria (20 listed)
- Treatment with an EGFR tyrosine kinase inhibitor (TKI) ≤ 8 days or 5x the terminal phase, elimination half-lives, whichever is shorter, prior to the first dose of study drug.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAY2927088_formulation AOral administration | Drug | Backfill, Dose escalation |
| BAY2927088_formulation B_1Oral administration | Drug | Backfill, Dose escalation, Dose expansion, Extension part |
| BAY2927088_formulation B_2Oral administration | Drug | Backfill, Dose escalation, Dose expansion, Extension part |
| BAY2927088_formulation B_3Oral administration | Drug | Dose expansion |
Primary outcome
Number of participants with treatment-emergent adverse events (TEAEs)
Time frame: Up to 30 days after the last administration of study treatment
Number of participants with treatment-emergent serious adverse events (TESAEs)
Time frame: Up to 30 days after the last administration of study treatment
Severity of TEAEs
Time frame: Up to 30 days after the last administration of study treatment
Severity of TESAEs
Time frame: Up to 30 days after the last administration of study treatment
Number of participants who discontinue study treatment due to an AE
Time frame: About 4 years (Up to the end of study treatment)
Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2927088 within the DLT observation period in Dose Escalation (including participants from Backfill qualifying for the MTD population)
Time frame: At the end of Cycle 1 of a 21-day cycle
Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY2927088 in the DLT observation period in Dose Escalation (including participants from Backfill)
Time frame: At the end of Cycle 1 of a 21-day cycle
In Dose Escalation (including participants from Backfill)
Cmax of BAY2927088
Time frame: Cycle 1, Day 1 (Cycle duration is 21 days)
Cmax: Maximum/peak concentration
AUC(0-24) of BAY2927088 for QD
Time frame: Cycle 1, Day 1 (Cycle duration is 21 days)
AUC: Area under the concentration vs. time curve. AUC(0-24): AUC from time 0 to 24 hours post dose. QD: Quaque die (once daily)
AUC(0-12) of BAY2927088 for BID
Time frame: Cycle 1, Day 1 (Cycle duration is 21 days)
If applicable. AUC(0-12): AUC from time 0 to 12 hours post dose. BID: Bis in die, 2 times daily.
Cmax,md of BAY2927088
Time frame: Cycle 1, Day 15 (Cycle duration is 21 days)
Cmax,md: Cmax after multiple dose administrations
AUC(0-24)md of BAY2927088 for QD
Time frame: Cycle 1, Day 15 (Cycle duration is 21 days)
AUC(0-24)md: AUC(0-24) after multiple dose administrations
AUC(0-12)md of BAY2927088 for BID
Time frame: Cycle 1, Day 15 (Cycle duration is 21 days)
If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR) in extension part
Time frame: From the start of the study treatment up to 12 months
8 secondary outcomes
Overall response rate (ORR) as per RECIST v1.1 by investigator assessment
Time frame: About 4 years
Recommended phase 2 dose (RP2D) of BAY2927088
Time frame: About 1.5 years
ORR per RECIST v1.1 by Investigator assessment in extension part
Time frame: From the start of the study treatment up to 12 months
Disease control rate (DCR) per RECIST v1.1 by Investigator assessment and BICR in extension part
Time frame: From the start of the study treatment up to 12 months
Duration of response (DOR) per RECIST 1.1 by Investigator assessment and BICR in extension part
Time frame: From the start of the study treatment up to 12 months
Progression-free survival (PFS) per RECIST 1.1 by Investigator assessment and BICR in extension part
Time frame: From the start of the study treatment up to 12 months
Overall survival (OS) in extension part
Time frame: From the start of the study treatment up to 12 months
Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity in extension part
Time frame: Up to 30 days after the last administration of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Derived from this study: PubMed 41104928Le 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 Nov 6;393(18):1819-1832. doi: 10.1056/NEJMoa2511065. Epub 2025 Oct 17.
- Individual participant dataSharing planned: No. Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
94 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BAY2927088_formulation A, BAY2927088_formulation B_1 and BAY2927088_formulation B_2 in people with Advanced Non-small Cell Lung Cancer and EGFR Mutation, run by Bayer at 94 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 94 sites in China, United States, Japan, Italy, France and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bayer Clinical Trials Contact (0018888422937, clinical-trials-contact@bayer.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-emergent adverse events (TEAEs) (time frame: Up to 30 days after the last administration of study treatment). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05099172, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.