Trial Condition(s):

Advanced Non-Small Cell Lung Cancer, EGFR mutation, HER2 mutation

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 Identifier:

21607

ClinicalTrials.gov Identifier:

NCT05099172

EudraCT Number:

2021-003022-77

EU CT Number:

2023-503795-24-00

Recruiting

Trial Purpose

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, 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 BAY 2927088
• The (average) highest level of BAY 2927088 in the blood (also called Cmax) after receiving a single or multiple doses of BAY2927088
Extension Part
• How well does BAY 2927088 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 BAY 2927088 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.

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. 
- 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. 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: 
a. 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. 
b. Platelets ≥ 100 × 10^9 cells/L. 
c. 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: 
a. 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). 
b. 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: 
a. Participants with treated brain metastases that are asymptomatic at screening and who are off or receiving low-dose of 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.
b. Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion 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 of corticosteroids (≤10 mg prednisone or equivalent) for 7 days prior to first dose of BAY2927088.
c. 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.
- 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: 
a. 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 
b. Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg]) and Hepatitis B virus [HBV] DNA). 
c. 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.

Trial Summary

Enrollment Goal
460
Trial Dates
black-arrow
Phase
1/2
Could I receive a placebo?
No
Products
BAY2927088
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

National Taiwan University Hospital

Taipei, Taiwan, China, 100

Status
Recruiting
Locations

Henry Ford Health System | Brigitte Harris Cancer Pavilion

Detroit, United States, 48202

Status
Recruiting
Locations

Dana-Farber Cancer Institute

Boston, United States, 02215

Status
Recruiting
Locations

City of Hope National Medical Center

Duarte, United States, 91010

Status
Recruiting
Locations

National University Hospital

Singapore, Singapore, 119074

Status
Recruiting
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National Cancer Center Singapore

Singapore, Singapore, 169610

Status
Recruiting
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Shanghai Chest Hospital, Shanghai Jiaotong University

Shanghai, China, 200030

Status
Recruiting
Locations

Beijing Cancer Hospital

Beijing, China, 100142

Status
Recruiting
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West China Hospital Sichuan University

Chengdu, China, 610041

Status
Recruiting
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Zhejiang Cancer Hospital

Hangzhou, China, 310022

Status
Recruiting
Locations

Prince of Wales Hospital

Shatin, Hong Kong, China

Status
Recruiting
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Emory University

Atlanta, United States, 30322

Status
Recruiting
Locations

University of Texas MD Anderson Cancer Center

Houston, United States, 77030

Status
Recruiting
Locations

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08023

Status
Recruiting
Locations

Institut Català d'Oncologia Hospitalet

Hospitalet de Llobregat, Spain, 08907

Status
Recruiting
Locations

Fundacion Jimenez Diaz (Clinica de la Concepcion)

Madrid, Spain, 28040

Status
Recruiting
Locations

Taichung Veterans General Hospital

Taichung, Taiwan, China, 40705

Status
Recruiting
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National Cancer Center Hospital East

Kashiwa, Japan, 277-8577

Status
Recruiting
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National Cancer Center Hospital

Chuo-ku, Japan, 104-0045

Status
Recruiting
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Shizuoka Cancer Center

Sunto, Japan, 411-8777

Status
Recruiting
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Asan Medical Center

Seoul, South Korea, 138-736

Status
Recruiting
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Seoul National University Hospital

Seoul, South Korea, 3080

Status
Recruiting
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Istituto Nazionale Tumori IRCCS Fondazione G.Pascale

Napoli, Italy, 80131

Status
Recruiting
Locations

IRCCS Centro di Riferimento Oncologico (CRO)

Pordenone, Italy, 33081

Status
Recruiting
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Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy, 00168

Status
Recruiting
Locations

Roswell Park Comprehensive Cancer Center

Buffalo, United States, 14203

Status
Suspended
Locations

Institut Gustave Roussy - Département de Médecine Oncologique

VILLEJUIF CEDEX, France, 94805

Status
Recruiting
Locations

Institut Bergonié - Unicancer Nouvelle Aquitaine

BORDEAUX CEDEX, France, 33076

Status
Recruiting
Locations

Institut Curie - Ulm - Paris

PARIS cedex 5, France, 75248

Status
Recruiting
Locations

Tottori University Hospital

Yonago, Japan, 683-8504

Status
Recruiting
Locations

Osaka International Cancer Institute

Osaka, Japan, 541-8567

Status
Recruiting
Locations

Seoul National University Bundang Hospital

Seongnam-si, South Korea, 13620

Status
Recruiting
Locations

Severance Hospital, Yonsei University Health System

Seoul, South Korea, 3722

Status
Recruiting
Locations

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

Wuhan, China, 430023

Status
Recruiting
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Hunan Cancer Hospital

Changsha, China, 410013

Status
Recruiting
Locations

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

Nanjing, China, 210008

Status
Recruiting
Locations

City of Hope-Cancer Department

Duarte, United States, 91010

Status
Recruiting
Locations

UZ Leuven Gasthuisberg

LEUVEN, Belgium, 3000

Status
Recruiting
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IPO Porto

Porto, Portugal, 4200-072

Status
Recruiting
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Centro Integral Oncológico Clara Campal

Madrid, Spain, 28050

Status
Recruiting
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Hospital Universitari i Politècnic La Fe

Valencia, Spain, 46026

Status
Recruiting
Locations

Hospital Quiron Dexeus

Barcelona, Spain, 08028

Status
Recruiting
Locations

AZ Delta | Clinical Trial Center - Pneumology

Roeselare, Belgium, 8800

Status
Recruiting
Locations

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland, 80-214

Status
Recruiting
Locations

SP ZOZ USK im. WAM UM w Lodzi - Centralny Szpital Weteranow

Lodz, Poland, 90-549

Status
Recruiting
Locations

Queen Mary Hospital

Hong Kong, Hong Kong, China

Status
Recruiting
Locations

Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.

Milano, Italy, 20089

Status
Recruiting
Locations

A.O.U. San Luigi Gonzaga

Torino, Italy, 10043

Status
Recruiting
Locations

A.O.U. di Parma

Parma, Italy, 43126

Status
Recruiting
Locations

IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)

Milano, Italy, 20141

Status
Recruiting
Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, Italy, 20133

Status
Recruiting
Locations

Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department

Sao Paulo, Brazil, 05651-901

Status
Recruiting
Locations

Harbin Medical University Cancer Hospital

Harbin, China, 150081

Status
Recruiting
Locations

Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine

Hangzhou, China, 310016

Status
Recruiting
Locations

Fujian Cancer Hospital

Fuzhou, China, 350014

Status
Recruiting
Locations

Qilu Hospital of Shandong University

Jinan, China

Status
Recruiting
Locations

Beijing Hospital

Beijing, China, 100730

Status
Recruiting
Locations

Centre Léon Bérard

lyon, France, 69008

Status
Recruiting
Locations

Institut de Cancérologie de l'Ouest - Saint Herblain

Saint-Herblain, France, 44800

Status
Recruiting
Locations

Banner MD Anderson Cancer Center

Gilbert, United States, 85234

Status
Recruiting
Locations

Virginia Cancer Specialists, PC

Fairfax, United States, 22031

Status
Recruiting
Locations

The Center for Cancer and Blood Disorders

Bethesda, United States, 20817

Status
Recruiting
Locations

Tennessee Oncology

Nashville, United States, 37203

Status
Recruiting
Locations

Chaim Sheba Medical Center

Ramat Gan, Israel, 5266202

Status
Recruiting
Locations

Clalit Health Services Rabin Medical Center-Beilinson Campus

Petah Tikva, Israel, 4941492

Status
Recruiting
Locations

Nederlands Kanker Instituut

AMSTERDAM, Netherlands, 1066 CX

Status
Recruiting
Locations

Erasmus Medisch Centrum

ROTTERDAM, Netherlands, 3015 GD

Status
Recruiting
Locations

Hokkaido University Hospital

Sapporo, Japan, 060-8648

Status
Recruiting
Locations

Kanagawa Cancer Center

Yokohama, Japan, 241-8515

Status
Recruiting
Locations

National Hospital Organization Shikoku Cancer Center

Matsuyama, Japan, 791-0280

Status
Recruiting
Locations

Aichi Cancer Center Hospital

Nagoya, Japan, 464-8681

Status
Recruiting
Locations

St.Vincent's Hospital

Suwon-si, South Korea, 442-723

Status
Recruiting
Locations

Chungbuk National University Hospital

Cheongju-si, South Korea, 28644

Status
Recruiting
Locations

Chang Gung Memorial Hospital at Linkou

Taoyuan, Taiwan, China, 33305

Status
Recruiting
Locations

National Cheng Kung University Hospital

Tainan, Taiwan, China, 704

Status
Recruiting
Locations

Hospital de Base | Integrated Research Center

São José do Rio Preto, Brazil, 15090-000

Status
Recruiting
Locations

Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica

Natal, Brazil, 59040-000

Status
Recruiting
Locations

START Lisbon, CHULN - Centro Hospitalar Universitário de Lisboa Norte

Lisbon, Portugal, 1649-028

Status
Not yet recruiting
Locations

Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital Nord

Marseille, France, 13915

Status
Not yet recruiting
Locations

Hôpital Nord Laennec - Oncologie médicale thoracique et digestive

Nantes, France, 44093

Status
Not yet recruiting
Locations

Curie Oncology

Singapore, Singapore, 329563

Status
Not yet recruiting
Locations

Hospital Universitario Virgen de la Victoria | Oncology

Mlaaga, Spain, 29010

Status
Not yet recruiting
Locations

Kindai University Hospital

Osakasayama-shi, Japan, 589-8511

Status
Not yet recruiting
Locations

Okayama University Hospital

Okayama-city, Japan, 700-8558

Status
Not yet recruiting
Locations

Radboud University Medical Center | Afdeling Interne Geneeskunde

Nijmegen, Netherlands, 6500 HB

Status
Not yet recruiting
Locations

Azienda Ospedaliera Universitaria Integrata Verona (AOUI)

Verona, Italy, 37126

Status
Not yet recruiting

Trial Design