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NCT05099172PHASE1, PHASE2Recruiting

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)

Bayer

Start Date

10/25/2021

Completion Date

6/29/2029

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. 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

Age Range: 18 years to No maximum

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.

Interventions

DRUG

BAY2927088_formulation A

DRUG

BAY2927088_formulation B_1

DRUG

BAY2927088_formulation B_2

DRUG

BAY2927088_formulation B_3

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Conditions

Advanced Non-small Cell Lung CancerEGFR MutationHER2 Mutation

Locations

Banner MD Anderson Cancer Center at Banner Gateway Medical Center

Gilbert, Arizona 85234

United States

City of Hope - Duarte Cancer Center

Duarte, California 91010

United States

Emory Winship Cancer Institute

Atlanta, Georgia 30322

United States

The Center for Cancer and Blood Disorders

Bethesda, Maryland 20817

United States

Dana-Farber Cancer Institute - Oncology Department

Boston, Massachusetts 02215

United States

Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit

Detroit, Michigan 48202

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York 14263

United States

NYU Langone Hospital - Long Island - Urology

Mineola, New York 11501

United States

Tennessee Oncology - Nashville Centennial Clinic

Nashville, Tennessee 37203

United States

The University of Texas MD Anderson Cancer Center - Texas Medical Center

Houston, Texas 77030

United States

Virginia Cancer Specialists, PC - Fairfax

Fairfax, Washington 22031

United States

UZ Leuven Gasthuisberg - Pneumology Department

Leuven, Flemish Brabant 3000

Belgium

AZ Delta | Clinical Trial Center - Pneumology

Roeselare, West Flanders 8800

Belgium

Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica

Natal, Rio Grande do Norte 59040-000

Brazil

Hospital de Base | Integrated Research Center

São José do Rio Preto, São Paulo 15090-000

Brazil

Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department

São Paulo, São Paulo 05651-901

Brazil

Beijing Cancer Hospital - Oncology Department

Beijing, Beijing Municipality 100142

China

Beijing Hospital

Beijing, Beijing Municipality 100730

China

Fujian Cancer Hospital

Fuzhou, Fujian 350014

China

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang 150000

China

Union Hospi, Tongji Med College, Huazhong Univ. Scien&Tech

Wuhan, Hubei 430023

China

Hunan Cancer Hospital - Oncology Department

Changsha, Hunan 410013

China

NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School

Nanjing, Jiangsu 210008

China

Zhejiang University School of Medicine - Taizhou Hospital of Zhejiang Province

Taizhou, Jiangsu 317000

China

Qilu Hosp., Shandong Univ.

Jinan, Shandong 250012

China

Shandong University - Shandong Cancer Hospital

Jinan, Shandong 250117

China

Shanghai Chest Hospital, Shanghai Jiaotong University

Shanghai, Shanghai Municipality 200030

China

West China Hospital Sichuan University

Chengdu, Sichuan 610041

China

Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department

Hangzhou, Zhejiang 310016

China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang 310022

China

UNICANCER - Centre Leon-Berard (CLB) - Medical oncology

Lyon, Auvergne-Rhône-Alpes 69373

France

Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale

Bordeaux, New Aquitaine 33000

France

Hopital Nord Laennec - Oncologie medicale thoracique et digestive

Nantes, Pays de la Loire Region 44093

France

Institut de Cancerologie Ouest - Saint Herblain - Oncologie medicale

Saint-Herblain, Pays de la Loire Region 44800

France

AP-HM - Hopital de la Timone - Centre d'Essais en Cancerologie

Marseille, Provence-Alpes-Côte d'Azur Region 13005

France

Institut Curie - Paris - Oncologie medicale

Paris, Île-de-France Region 75248

France

Gustave Roussy - Departement Oncologie-Radiotherapie

Villejuif, Île-de-France Region 94805

France

Prince of Wales Hospital

Hong Kong, Hong Kong SAR 00000

Hong Kong

Queen Mary Hospital

Hong Kong, Hong Kong SAR 00000

Hong Kong

Hong Kong United Oncology Centre

Kowloon, 00000

Hong Kong

Rabin Medical Center | Beilinson Hospital - Nephrology and Hypertension Institute

Petah Tikva, 4941492

Israel

Chaim Sheba Medical Center

Ramat Gan, 5262000

Israel

Istituto Nazionale Tumori IRCCS Fondazione G.Pascale

Naples, Campania 80131

Italy

Azienda Ospedaliero Universitaria Parma - SC Oncologia Medica

Parma, Emilia-Romagna 43126

Italy

Centro di Riferimento Oncologico di Aviano - Oncologia Medica e dei Tumori Immuno-Correlati

Aviano, Friuli Venezia Giulia 33081

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I

Rome, Lazio 00128

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1

Milan, Lombardy 20133

Italy

Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative

Milan, Lombardy 20141

Italy

Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia

Rozzano, Lombardy 20089

Italy

Azienda Ospedaliero-Universitaria San Luigi Gonzaga - Oncologia Medica

Orbassano, Piedmont 10043

Italy

Centro Ricerche Cliniche Di Verona S.r.l. - Oncologia

Verona, 37134

Italy

Aichi Cancer Center Hospital

Nagoya, Aichi-ken 464-8681

Japan

National Cancer Center Hospital East

Kashiwa, Chiba 277-8577

Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime 791-0280

Japan

Hokkaido University Hospital

Sapporo, Hokkaido 060-8648

Japan

Kanagawa Cancer Center

Yokohama, Kanagawa 241-8515

Japan

Kindai University Hospital

Sakai, Osaka 590-0197

Japan

Shizuoka Cancer Center

Sunto, Shizuoka 411-8777

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

Tottori University Hospital

Yonago, Tottori 683-8504

Japan

Okayama University Hospital

Okayama, 700-8558

Japan

Osaka International Cancer Institute

Osaka, 541-8567

Japan

Radboud University Medical Center | Afdeling Interne Geneeskunde

Nijmegen, Gelderland 6500 HB

Netherlands

Nederlands Kanker Instituut

Amsterdam, North Holland 1066 CX

Netherlands

Erasmus University Medical Center | Research Department - Lung Diseases

Rotterdam, South Holland 3015 GD

Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214

Poland

Uniwersytecki Szpital Kliniczny Nr 2 Uniwersytetu Medycznego w Lodzi

Lodz, 92-213

Poland

START Lisbon, CHULN - Centro Hospitalar Universitário de Lisboa Norte

Lisbon, 1649-028

Portugal

Hospital Santa Maria | Centro de Investigacao Clinica

Lisbon, 1649-035

Portugal

IPO Porto

Porto, 4200-072

Portugal

National University Hospital Medical Centre

Singapore, 119074

Singapore

National Cancer Center Singapore - Oncology Department

Singapore, 168583

Singapore

Curie Oncology | Mount Elizabeth Novena

Singapore, 329563

Singapore

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do 13620

South Korea

St.Vincent's Hospital

Suwon, Gyeonggi-do 16247

South Korea

Chungbuk National University Hospital | Hematology and Oncology

Chungcheongbuk-do, North Chungcheong 28644

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital, Yonsei University Health System - Oncology Department

Seoul, 03722

South Korea

Asan Medical Center | Oncology

Seoul, 05505

South Korea

Samsung Medical Center - Oncology Department

Seoul, 06351

South Korea

Institut Catala D'oncologia | Hospitalet | Oncologia

L'Hospitalet de Llobregat, Barcelona 08908

Spain

Hospital Universitari Dexeus Grupo Quironsalud | Oncologia

Barcelona, 08028

Spain

Hospital Universitari Vall D Hebron | Oncologia

Barcelona, 08035

Spain

Hospital Universitario Fundacion Jimenez Diaz | Oncologia

Madrid, 28040

Spain

Hospital Universitario Hm Sanchinarro | Oncologia

Madrid, 28050

Spain

Hospital Universitario Virgen De La Victoria | Oncologia

Málaga, 29010

Spain

Hospital Universitario Y Politecnico La Fe | Oncologia

Valencia, 46026

Spain

Chung Shan Medical University Hospital

Taichung, 402306

Taiwan

Taichung Veterans General Hospital

Taichung, 40705

Taiwan

National Cheng Kung University Hospital

Tainan, 704

Taiwan

Chi-Mei Medical Center, Liouyine

Tainan, 73657

Taiwan

National Taiwan University Hospital

Taipei, 100

Taiwan

Taipei Medical University (TMU) - Shuang Ho Hospital (SHH)

Taipei, 23561

Taiwan

Chang Gung Memorial Hospital at Linkou

Taoyuan, 33305

Taiwan