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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)

NCT05099172 · Bayer
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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
About this study
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.
Eligibility criteria
Inclusion Criteria: * 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 and Group H (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 and Group H, 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 × 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 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). * 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 sevabertinib 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 and Group 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. 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 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: 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.
Study design
Enrollment target: 400 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2021-10-25
Estimated completion: 2031-06-30
Last updated: 2026-08-12
Interventions
Drug: BAY2927088_formulation ADrug: BAY2927088_formulation B_1Drug: BAY2927088_formulation B_2Drug: BAY2927088_formulation B_3
Primary outcomes
  • Number of participants with treatment-emergent adverse events (TEAEs) (Up to 30 days after the last administration of study treatment)
  • Number of participants with treatment-emergent serious adverse events (TESAEs) (Up to 30 days after the last administration of study treatment)
  • Severity of TEAEs (Up to 30 days after the last administration of study treatment)
Sponsor
Bayer · industry
Contacts & investigators
ContactBayer Clinical Trials Contact · contact · clinical-trials-contact@bayer.com · 0018888422937
All locations (92)
Banner MD Anderson Cancer Center at Banner Gateway Medical CenterCompleted
Gilbert, Arizona, United States
City of Hope - Duarte Cancer CenterCompleted
Duarte, California, United States
Emory Winship Cancer InstituteActive Not Recruiting
Atlanta, Georgia, United States
The Center for Cancer and Blood DisordersWithdrawn
Bethesda, Maryland, United States
Dana-Farber Cancer Institute - Oncology DepartmentCompleted
Boston, Massachusetts, United States
Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - DetroitCompleted
Detroit, Michigan, United States
Roswell Park Comprehensive Cancer CenterWithdrawn
Buffalo, New York, United States
Tennessee Oncology - Nashville Centennial ClinicRecruiting
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center - Texas Medical CenterActive Not Recruiting
Houston, Texas, United States
Inova Schar Cancer Insitute - Inova Fairfax HospitalWithdrawn
Fairfax, Washington, United States
Virginia Cancer Specialists, PC - FairfaxCompleted
Fairfax, Washington, United States
UZ Leuven Gasthuisberg - Pneumology DepartmentActive Not Recruiting
Leuven, Flemish Brabant, Belgium
AZ Delta | Clinical Trial Center - PneumologyActive Not Recruiting
Roeselare, West Flanders, Belgium
Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa ClínicaActive Not Recruiting
Natal, Rio Grande do Norte, Brazil
Hospital de Base | Funfarme - Centro Integrado de Pesquisa - CardiologiaWithdrawn
São José do Rio Preto, São Paulo, Brazil
Hospital Israelita Albert Einstein | Morumbi - Clinical Research DepartmentWithdrawn
São Paulo, Brazil
Beijing Cancer Hospital - Oncology DepartmentActive Not Recruiting
Beijing, Beijing Municipality, China
Beijing HospitalActive Not Recruiting
Beijing, Beijing Municipality, China
Fujian Cancer HospitalActive Not Recruiting
Fuzhou, Fujian, China
Harbin Medical University Cancer HospitalTerminated
Harbin, Heilongjiang, China
Union Hospi, Tongji Med College, Huazhong Univ. Scien&TechActive Not Recruiting
Wuhan, Hubei, China
Hunan Cancer Hospital - Oncology DepartmentActive Not Recruiting
Changsha, Hunan, China
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med SchoolActive Not Recruiting
Nanjing, Jiangsu, China
Zhejiang University School of Medicine - Taizhou Hospital of Zhejiang ProvinceActive Not Recruiting
Taizhou, Jiangsu, China
Qilu Hosp., Shandong Univ.Terminated
Jinan, Shandong, China
Shandong University - Shandong Cancer HospitalActive Not Recruiting
Jinan, Shandong, China
Shanghai Chest Hospital, Shanghai Jiaotong UniversityActive Not Recruiting
Shanghai, Shanghai Municipality, China
West China Hospital Sichuan UniversityActive Not Recruiting
Chengdu, Sichuan, China
Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology DepartmentActive Not Recruiting
Hangzhou, Zhejiang, China
Zhejiang Cancer HospitalActive Not Recruiting
Hangzhou, Zhejiang, China
UNICANCER - Centre Leon-Berard (CLB) - Medical oncologyActive Not Recruiting
Lyon, Auvergne-Rhône-Alpes, France
Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicaleCompleted
Bordeaux, New Aquitaine, France
Hopital Nord Laennec - Oncologie medicale thoracique et digestiveActive Not Recruiting
Nantes, Pays de la Loire Region, France
Institut de Cancerologie Ouest - Saint Herblain - Oncologie medicaleActive Not Recruiting
Saint-Herblain, Pays de la Loire Region, France
AP-HM - Hopital de la Timone - Centre d'Essais en CancerologieWithdrawn
Marseille, Provence-Alpes-Côte d'Azur Region, France
Institut Curie - Paris - Oncologie medicaleCompleted
Paris, Île-de-France Region, France
Gustave Roussy - Departement Oncologie-RadiotherapieCompleted
Villejuif, Île-de-France Region, France
Prince of Wales HospitalActive Not Recruiting
Hong Kong, Hong Kong SAR, Hong Kong
Queen Mary HospitalActive Not Recruiting
Hong Kong, Hong Kong SAR, Hong Kong
Hong Kong United Oncology CentreRecruiting
Kowloon, Hong Kong
Rabin Medical Center | Beilinson CampusCompleted
Petah Tikva, Israel
Chaim Sheba Medical CenterCompleted
Ramat Gan, Israel
Centro di Riferimento Oncologico di Aviano - Oncologia Medica e dei Tumori Immuno-CorrelatiActive Not Recruiting
Aviano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1Active Not Recruiting
Milan, Italy
Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie InnovativeCompleted
Milan, Italy
Azienda Ospedaliero-Universitaria San Luigi Gonzaga - Oncologia MedicaActive Not Recruiting
Orbassano, Italy
Azienda Ospedaliero Universitaria Parma - SC Oncologia MedicaActive Not Recruiting
Parma, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase IActive Not Recruiting
Roma, Italy
Humanitas Mirasole S.p.A. - Oncologia Medica ed EmatologiaActive Not Recruiting
Rozzano, Italy
Centro Ricerche Cliniche Di Verona S.r.l. - OncologiaCompleted
Verona, Italy
Aichi Cancer Center HospitalActive Not Recruiting
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital EastActive Not Recruiting
Kashiwa, Chiba, Japan
National Hospital Organization Shikoku Cancer CenterCompleted
Matsuyama, Ehime, Japan
Hokkaido University HospitalActive Not Recruiting
Sapporo, Hokkaido, Japan
Kanagawa Cancer CenterActive Not Recruiting
Yokohama, Kanagawa, Japan
Kindai University HospitalActive Not Recruiting
Sakai, Osaka, Japan
Shizuoka Cancer CenterCompleted
Sunto, Shizuoka, Japan
National Cancer Center HospitalActive Not Recruiting
Chuo-ku, Tokyo, Japan
Tottori University HospitalCompleted
Yonago, Tottori, Japan
Okayama University HospitalTerminated
Okayama, Japan
Osaka International Cancer InstituteActive Not Recruiting
Osaka, Japan
Radboud University Medical Center | Afdeling Interne GeneeskundeWithdrawn
Nijmegen, Gelderland, Netherlands
Nederlands Kanker InstituutActive Not Recruiting
Amsterdam, North Holland, Netherlands
Erasmus University Medical Center | Research Department - Lung DiseasesCompleted
Rotterdam, South Holland, Netherlands
Uniwersyteckie Centrum KliniczneWithdrawn
Gdansk, Poland
Uniwersytecki Szpital Kliniczny Nr 2 Uniwersytetu Medycznego w ŁodziWithdrawn
Lodz, Poland
START Research PortugalWithdrawn
Lisbon, Portugal
IPO PortoRecruiting
Porto, Portugal
National University Hospital Medical CentreActive Not Recruiting
Singapore, Singapore
National Cancer Center Singapore - Oncology DepartmentActive Not Recruiting
Singapore, Singapore
Curie Oncology | Mount Elizabeth NovenaActive Not Recruiting
Singapore, Singapore
Seoul National University Bundang Hospital | Hematology and Medical OncologyCompleted
Seongnam-si, Gyeonggi-do, South Korea
St Vincent's Hospital | OncologyActive Not Recruiting
Suwon, Gyeonggi-do, South Korea
Chungbuk National University Hospital | Hematology and OncologyActive Not Recruiting
Chungcheongbuk-do, North Chungcheong, South Korea
Seoul National University Hospital | OncologyActive Not Recruiting
Jongno -Gu, Seoul, South Korea
Severance Hospital | OncologyActive Not Recruiting
Seoul, South Korea
Asan Medical Center | OncologyActive Not Recruiting
Seoul, South Korea
Samsung Medical Center | OncologyActive Not Recruiting
Seoul, South Korea
Institut Catala D'oncologia | Hospitalet | OncologiaActive Not Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitari Dexeus Grupo Quironsalud | OncologiaActive Not Recruiting
Barcelona, Spain
Hospital Universitari Vall D Hebron | OncologiaActive Not Recruiting
Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz | OncologiaActive Not Recruiting
Madrid, Spain
Hospital Universitario Hm Sanchinarro | OncologiaCompleted
Madrid, Spain
Hospital Universitario Virgen De La Victoria | OncologiaWithdrawn
Málaga, Spain
Hospital Universitario Y Politecnico La Fe | OncologiaActive Not Recruiting
Valencia, Spain
Chung Shan Medical University HospitalWithdrawn
Taichung, Taiwan
Taichung Veterans General HospitalActive Not Recruiting
Taichung, Taiwan
National Cheng Kung University HospitalActive Not Recruiting
Tainan, Taiwan
Chi-Mei Medical Center, LiouyineActive Not Recruiting
Tainan, Taiwan
National Taiwan University HospitalActive Not Recruiting
Taipei, Taiwan
Taipei Medical University (TMU) - Shuang Ho Hospital (SHH)Withdrawn
Taipei, Taiwan
Chang Gung Memorial Hospital at LinkouActive Not Recruiting
Taoyuan, Taiwan
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) · TrialPath