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)

Advanced Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05099172
• Other study ID #: 21607
• Secondary ID: 2023-503795-24-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 25, 2021
• Est. completion date: November 30, 2027

Study information

• Verified date: May 2024
• Source: Bayer
• Contact: Bayer Clinical Trials Contact
• Phone: (+)1-888-84 22937
• Email: clinical-trials-contact[@]bayer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 370
• Est. completion date: November 30, 2027
• Est. primary completion date: November 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 one of the groups (Expansion or Extension) who should have received no prior systemic treatment for locally advanced or metastatic disease.

• Adequate archival tumor tissue (ideally taken after last targeted treatment and not older than 6 months) has to be available, either from primary or metastatic sites. If archival material is not available, a fresh tumor biopsy should be performed if feasible and if the procedure poses no significant risk for the participant.

• Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy during the screening period (if a biopsy is taken during screening) that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied lesion should not be used as a target lesion for RECIST 1.1 tumor assessments (or, for participants in Expansion Group G, for RANO-BM tumor assessments). Previously irradiated lesions must have shown progression to be considered measurable.

• Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (United States [US] sites) or an equally accredited (outside of the US) local laboratory

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

• Minimum life expectancy of 12 weeks.

• Adequate bone marrow function as assessed by the following laboratory tests to be conducted within 7 days before the first dose of study treatment:

1. Hemoglobin = 9.0 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.

2. Platelets = 100 × 10^9 cells/L.

3. Absolute neutrophil count = 1.5 ×10^9 cells/L. Criteria must be met without the use of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to testing.

• Adequate kidney function as assessed by following laboratory test to be conducted within 7 days before the first dose of study treatment:

a. Estimated glomerular filtration rate (eGFR) > 50 mL/min per 1.73 m^2 according to the Modification of Diet in renal Disease Study Group (MDRD) formula.

• Adequate liver function as assessed by following laboratory tests to be conducted within 7 days before the first dose of study treatment:

1. Total bilirubin = 1.5 × ULN (or = 3 X ULN for participants with documented Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia considered due to liver metastasis).

2. Aspartate transaminase and alanine transaminase = 2.5 × ULN (or = 5 × ULN if due to liver involvement by tumor).

Exclusion Criteria:

• Treatment with 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 BAY 2927088 are eligible to enroll in Dose Escalation and Backfill.

2. Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion/Extension (with the exception of Group G) if all of the following criteria are met:

• there is no evidence of progression (new or enlarging brain metastases) for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.

• Participants must be off or receiving low-dose corticosteroids (=10 mg prednisone or equivalent) for 7 days prior to first dose of BAY2927088.

3. Participants with history of spinal cord compression >3 months from definitive therapy and stable by imaging (MRI or CT) during the screening period and clinically asymptomatic.

4. Expansion Group G only: Participants with active (new or progressing) clinically stable brain metastases who do not require immediate CNS-directed treatment as per Investigator's judgement and who are off or receiving low-dose corticosteroids (=10 mg prednisone or equivalent such as = 1.5 mg/day dexamethasone) in the 7 days prior to first dose of BAY2927088 are eligible.

• History of congestive heart failure (CHF) Class >II according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment (e.g. ventricular arrhythmias, atrial fibrillation) or any clinically important abnormalities in rhythm, conduction or morphology or resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec)

• Participants with:

1. Known human immunodeficiency virus (HIV), except as noted below: Participants with history of HIV infection are eligible at the Investigator's discretion provided that: • CD4+ T-cell (CD4+) counts are = 350 cells/uL • The participant has been on established antiretroviral therapy (ART) for at least 4 weeks prior to the start of study drug and has an HIV viral load less than 400 copies/mL prior to start of the study treatment • The ART being used does not contain strong inducers or inhibitors of CYP3A4, and is not anticipated to cause overlapping toxicities with study drug • The participant has not had an opportunistic infection within the past 12 months

2. Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg]) and Hepatitis B virus [HBV] DNA).

3. Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA results greater than the lower limits of detection of the assay).

NOTE: Participants with history of chronic HBV or HCV infection are eligible at the Investigator's discretion provided that the disease is stable and sufficiently controlled under treatment.

• Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first administration of study drug. Strong CYP3A4 inhibitors and inducers are prohibited during the study and until Safety FU (follow up) visit.

Related Conditions & MeSH terms

• Advanced Non-small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• EGFR Mutation
• Lung Neoplasms

Intervention

Drug:
• BAY2927088_formulation A
Oral administration
• BAY2927088_formulation B_1
Oral administration
• BAY2927088_formulation B_2
Oral administration

Locations

Country	Name	City	State
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	AZ Delta | Clinical Trial Center - Pneumology	Roeselare
Brazil	Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica	Natal	Rio Grande Do Norte
Brazil	Hospital de Base | Integrated Research Center	São José do Rio Preto	Sao Paulo
Brazil	Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department	Sao Paulo
China	Beijing Cancer Hospital	Beijing
China	Beijing Hospital	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Qilu Hosp., Shandong Univ.	Jinan	Shandong
China	Shandong University - Shandong Cancer Hospital	Jinan
China	NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School	Nanjing	Jiangsu
China	Shanghai Chest Hospital, Shanghai Jiaotong University	Shanghai
China	Zhejiang University School of Medicine - Taizhou Hospital of Zhejiang Province	Taizhou
China	Union Hospi, Tongji Med College, Huazhong Univ. Scien&Tech	Wuhan	Hubei
France	Institut Bergonié - Unicancer Nouvelle Aquitaine	Bordeaux Cedex
France	Centre Léon Bérard	Lyon
France	Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital Nord	Marseille
France	Hôpital Nord Laennec - Oncologie médicale thoracique et digestive	Nantes
France	Institut Curie - Ulm - Paris	PARIS cedex 5
France	Institut de Cancérologie de l'Ouest - Saint Herblain	Saint-Herblain
France	Institut Gustave Roussy - Département de Médecine Oncologique	Villejuif Cedex
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Hong Kong United Oncology Centre	Kowloon
Hong Kong	Prince of Wales Hospital	Shatin
Israel	Clalit Health Services Rabin Medical Center-Beilinson Campus	Petah Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)	Milano	Lombardia
Italy	Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione G.Pascale	Napoli	Campania
Italy	A.O.U. di Parma	Parma	Emilia-Romagna
Italy	IRCCS Centro di Riferimento Oncologico (CRO)	Pordenone	Friuli-Venezia Giulia
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Lazio
Italy	A.O.U. San Luigi Gonzaga	Torino	Piemonte
Italy	Azienda Ospedaliera Universitaria Integrata Verona (AOUI)	Verona
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Okayama University Hospital	Okayama-city	Okayama
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital	Osakasayama-shi
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Shizuoka Cancer Center	Sunto	Shizuoka
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Japan	Tottori University Hospital	Yonago	Tottori
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbugdo
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	St.Vincent's Hospital	Suwon-si	Gyeonggido
Netherlands	Nederlands Kanker Instituut	Amsterdam
Netherlands	Radboud University Medical Center | Afdeling Interne Geneeskunde	Nijmegen
Netherlands	Erasmus Medisch Centrum	Rotterdam
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	SP ZOZ USK im. WAM UM w Lodzi - Centralny Szpital Weteranow	Lodz
Portugal	CHULN - H. Sta.Maria (Centro de Investigacao Clinica)	Lisboa
Portugal	START Lisbon, CHULN - Centro Hospitalar Universitário de Lisboa Norte	Lisbon	Lisboa
Portugal	IPO Porto	Porto
Singapore	Curie Oncology	Singapore
Singapore	National Cancer Center Singapore	Singapore
Singapore	National University Hospital	Singapore
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital Quiron Dexeus	Barcelona
Spain	Institut Català d'Oncologia Hospitalet	Hospitalet de Llobregat	Barcelona
Spain	Centro Integral Oncológico Clara Campal	Madrid
Spain	Fundacion Jimenez Diaz (Clinica de la Concepcion)	Madrid
Spain	Hospital Universitario Virgen de la Victoria | Oncology	Málaga
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi-Mei Medical Center, Liouyine	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Medical University (TMU) - Shuang Ho Hospital (SHH)	Taipei
Taiwan	Chang Gung Memorial Hospital at Linkou	Taoyuan
United States	Emory University	Atlanta	Georgia
United States	The Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Henry Ford Health System | Brigitte Harris Cancer Pavilion	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	City of Hope-Cancer Department	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology	Nashville	Tennessee
United States	NYU Langone Health	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  China,  France,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events (TEAEs)		Up to 30 days after the last administration of study treatment
Primary	Number of participants with treatment-emergent serious adverse events (TESAEs)		Up to 30 days after the last administration of study treatment
Primary	Severity of TEAEs		Up to 30 days after the last administration of study treatment
Primary	Severity of TESAEs		Up to 30 days after the last administration of study treatment
Primary	Number of participants who discontinue study treatment due to an AE		About 4 years (Up to the end of study treatment)
Primary	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)		At the end of Cycle 1 of a 21-day cycle
Primary	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)	At the end of Cycle 1 of a 21-day cycle
Primary	Cmax of BAY2927088	Cmax: Maximum/peak concentration	Cycle 1, Day 1 (Cycle duration is 21 days)
Primary	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)	Cycle 1, Day 1 (Cycle duration is 21 days)
Primary	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.	Cycle 1, Day 1 (Cycle duration is 21 days)
Primary	Cmax,md of BAY2927088	Cmax,md: Cmax after multiple dose administrations	Cycle 1, Day 15 (Cycle duration is 21 days)
Primary	AUC(0-24)md of BAY2927088 for QD	AUC(0-24)md: AUC(0-24) after multiple dose administrations	Cycle 1, Day 15 (Cycle duration is 21 days)
Primary	AUC(0-12)md of BAY2927088 for BID	If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations	Cycle 1, Day 15 (Cycle duration is 21 days)
Primary	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		From the start of the study treatment up to 12 months
Secondary	Overall response rate (ORR) as per RECIST v1.1 by investigator assessment	RECIST v1.1: Response Evaluation Criteria in Solid Tumors, version 1.1	About 4 years
Secondary	Recommended phase 2 dose (RP2D) of BAY2927088		About 1.5 years
Secondary	ORR per RECIST v1.1 by Investigator assessment in extension part		From the start of the study treatment up to 12 months
Secondary	Disease control rate (DCR) per RECIST v1.1 by Investigator assessment and BICR in extension part		From the start of the study treatment up to 12 months
Secondary	Duration of response (DOR) per RECIST 1.1 by Investigator assessment and BICR in extension part		From the start of the study treatment up to 12 months
Secondary	Progression-free survival (PFS) per RECIST 1.1 by Investigator assessment and BICR in extension part		From the start of the study treatment up to 12 months
Secondary	Overall survival (OS) in extension part		From the start of the study treatment up to 12 months
Secondary	Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity in extension part		Up to 30 days after the last administration of study treatment

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