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Advanced solid tumors, HER2 mutation

A study to learn more about how well treatment with BAY2927088 tablets works and how safe it is in participants who have a solid tumor with mutations of the human epidermal growth factor receptor 2 (HER2)

Trial purpose

Researchers are looking for a better way to treat people who have solid tumors with HER2-activating mutations. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it works.
In this trial, the researchers want to learn how well BAY2927088 works in people with different types of solid tumors with HER2 mutations. These include tumors in the colon or rectum, the uterus and the cervix (lower part of the uterus), the bladder, and the biliary tract (includes gall bladder and bile ducts) as well as other types of solid tumors with the exception of people with advanced non-small cell lung cancer (NSCLC).
Solid tumors may have specific changes or mutations to a gene called human epidermal growth receptor-2 (HER2). This leads to the formation of an abnormal form of HER2 protein in the cancer cells, resulting in increased cell growth. The study treatment, BAY2927088, is expected to block the abnormal HER2 protein which may stop the spread of cancer.
The trial will include about 111 participants who are at least 18 years old. All the participants will take 20 mg of BAY2927088 as tablets by mouth.
The participants will take treatments in 3-week periods called cycles. These 3-week cycles will be repeated throughout the trial. The participants can take BAY2927088 until their cancer gets worse, until they have medical problems, or until they leave the trial.
During the trial, the doctors will take imaging scans of different parts of the body to study the spread of cancer and will check heart health using echocardiogram or cardiac magnetic resonance imaging (MRI) and electrocardiogram (ECG). The doctors will also take blood and urine samples and do physical examinations to check the participants' health. They will ask questions about how the participants are feeling and if they have any medical problems.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - Documented histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumor cancer (colorectal carcinoma; biliary tract cancer; bladder and urothelial tract cancer; cervical cancer; endometrial cancer; other solid tumor cancer, excluding NSCLC)
    - Participant must be ≥18 years of age or over the legal age of consent
    - Patients who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments
    - Documented activating HER2 mutation
    - At least one measurable lesion that would qualify as a target lesion by RECIST 1.1 criteria
  • - Primary diagnosis of non-small cell lung cancer (NSCLC)
    - Prior treatment with a HER2 tyrosine kinase inhibitor (TKI)
    - Active brain metastases
    - Uncontrolled, severe, intercurrent illness

Trial summary

Enrollment Goal
111
Trial Dates
February 2025 - October 2027
Phase
Phase 2
Could I Receive a placebo
No
Products
BAY2927088
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Not yet recruiting
Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicaleBordeaux, 33000, France
Not yet recruiting
SCRI Oncology PartnersNashville, 37203, United States
Not yet recruiting
National Cancer Center Hospital East (NCCHE) - Kashiwa CampusKashiwa, 277-8577, Japan
Not yet recruiting
Centre Oscar Lambret - Service OncologieLille, 59000, France
Recruiting
Beijing Cancer HospitalBeijing, 100142, China
Recruiting
Rigshospitalet - KræftbehandlingCopenhagen OE, 2100, Denmark
Not yet recruiting
Princess Margaret Cancer Centre – University Health Network - Department of Medical Oncology and HematologyToronto, M5G 2C4, Canada
Not yet recruiting
Queen Elizabeth II Health Sciences Centre - Victoria General SiteHalifax, B3H 1V7, Canada
Recruiting
University of Texas MD Anderson Cancer CenterHouston, 77030-4000, United States
Not yet recruiting
Institut Catala d'Oncologia (ICO) - Hospital Duran i ReynalsL'Hospitalet de Llobregat, 08908, Spain
Not yet recruiting
Universidad de Navarra - Clinica Universidad de Navarra (CUN) - MadridMadrid, 28027, Spain
Not yet recruiting
Fundacion Jimenez Diaz (Clinica de la Concepcion)Madrid, 28040, Spain
Not yet recruiting
Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)Barcelona, 8035, Spain
Not yet recruiting
McGill University Health Centre – Glen SiteMontreal, H4A 3J1, Canada
Not yet recruiting
Aarhus University HospitalAarhus N, 8200, Denmark
Not yet recruiting
Odense University Hospital - Oncology DepartmentOdense C, 5000, Denmark
Withdrawn
University of Washington Medical Center (UWMC) - Montlake - Gynecology OncologySeattle, 98195-0001, United States
Not yet recruiting
Fudan University Shanghai Cancer CenterShanghai, 200000, China
Not yet recruiting
Hunan Cancer HospitalChangsha, 410013, China
Recruiting
Asan Medical CenterSeoul, 05505, Korea,_republic_of
Not yet recruiting
Samsung Medical CenterSeoul, 06351, Korea,_republic_of
Not yet recruiting
Seoul National University HospitalSeoul, 3080, Korea,_republic_of
Not yet recruiting
Severance Hospital, Yonsei University Health SystemSeoul, 03722, Korea,_republic_of
Not yet recruiting
UW Health - UW Carbone Cancer Center - Medical Oncology ClinicMadison, 53792, United States
Not yet recruiting
City of Hope - Duarte Cancer CenterDuarte, 91010, United States
Not yet recruiting
Centre Hospitalier Lyon Sud - Service oncologie medicalePierre-Benite, 69310, France
Recruiting
CHU Brest - Hopital La Cavale Blanche - service oncologie medicaleBrest, 29200, France
Not yet recruiting
Hokkaido University HospitalSapporo, 060-8648, Japan
Not yet recruiting
Aichi Cancer Center HospitalNagoya, 464-8681, Japan
Not yet recruiting
The Cancer Institute Hospital of JFCRKoto-ku, 135-8550, Japan
Not yet recruiting
Kindai University HospitalOsakasayama, 589-8511, Japan
Not yet recruiting
National Cancer Center HospitalChuo-ku, 104-0045, Japan
Not yet recruiting
Azienda USL IRCCS di Reggio Emilia_Arcispedale Santa Maria Nuova - S.C. Oncologia ProvincialeReggio Emilia, 42123, Italy
Not yet recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1Milano, 20133, Italy
Not yet recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia MedicaRoma, 00168, Italy
Not yet recruiting
Zhongshan Hospital, Fudan UniversityShanghai, 200032, China
Not yet recruiting
Sir Run Run Shaw Hospital, Zhejiang Univ. School of MedicineHangzhou, 310016, China
Not yet recruiting
Macquarie University HospitalSydney, 2109, Australia
Not yet recruiting
Dana-Farber Cancer InstituteBoston, 02215, United States
Not yet recruiting
Peking University First HospitalBeijing, 100034, China
Not yet recruiting
Univestitätsspital Zürich (USZ)Zürich, 8091, Switzerland
Not yet recruiting
Inselspital Bern - Universitätsklinik für Medizinische OnkologieBern, 3010, Switzerland
Not yet recruiting
Profound Research LLCFarmington Hills, 48334, United States
Not yet recruiting
Hopitaux Universitaires de GeneveGenève, 1205, Switzerland
Not yet recruiting
ICON Cancer Centre - SouthportSouthport, 4215, Australia
Not yet recruiting
Blacktown Cancer & Haematology CentreBlacktown, 2148, Australia
Withdrawn
Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - DetroitDetroit, 48202, United States
Not yet recruiting
Florida Cancer Specialists & Research Institute - Fort Myers Cancer Center - GladiolusFort Myers, 33908, United States
Not yet recruiting
Cleveland ClinicCleveland, 44195, United States
Not yet recruiting
University of Alabama at BirminghamBirmingham, 35233, United States

Primary Outcome

  • Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR
    ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) per RECIST 1.1 by BICR. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of <10 mm. PR is defined as a ≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR)
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first

Secondary Outcome

  • Duration of response (DOR) per RECIST 1.1 as assessed by BICR
    DOR is defined as the time from date of first documented complete or partial response (if confirmed) until the earliest date of progressive disease (PD) per RECIST 1.1 as assessed by BICR, or death from any cause, whichever occurs first. PD is defined as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR)
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • Time to response (TTR) per RECIST 1.1 as assessed by BICR
    TTR is defined as the time from the start of study treatment until the date of first documented complete or partial response (if confirmed) per RECIST 1.1 as assessed by BICR. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR)
    date_rangeTime Frame:
    From first participant enrolled until end of treatment or end of imaging active follow-up (up to approximately 3 years)
  • ORR per RECIST 1.1 as assessed by the investigator
    ORR is defined as the proportion of participants with a best overall response of confirmed CR or confirmed PR per RECIST 1.1 by investigator. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • Disease control rate (DCR) per RECIST 1.1 as assessed by BICR
    DCR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD), by the BICR per RECIST 1.1. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • DCR ≥12 weeks per RECIST 1.1 as assessed by BICR
    Defined as the proportion of participants with a best overall response of confirmed CR or PR or SD (for at least 12 weeks following the first study intervention), by the BICR per RECIST 1.1.
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • Progression-free survival (PFS) per RECIST 1.1 as assessed by BICR
    Defined as the time from date of start of treatment until the earliest date of PD per RECIST 1.1 as assessed by the BICR, or death from any cause, whichever occurs first.
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • Disease control rate (DCR) per RECIST 1.1 as assessed by the investigator
    Defined as the proportion of participants with a best overall response of confirmed CR or PR or SD, by the investigator per RECIST 1.1.
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • DCR ≥12 weeks per RECIST 1.1 as assessed by the investigator
    Defined as the proportion of participants with a best overall response of confirmed CR or PR or SD (for at least 12 weeks following the first study intervention), by the investigator per RECIST 1.1.
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • Progression-free survival (PFS) per RECIST 1.1 as assessed by the investigator
    Defined as the time from date of start of treatment until the earliest date of PD per RECIST 1.1 as assessed by the investigator, or death from any cause, whichever occurs first
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • DOR per RECIST 1.1 as assessed by the investigator
    DOR is defined as the time from date of first documented complete or partial response (if confirmed) until the earliest date of PD per RECIST 1.1 as assessed by the investigator, or death from any cause, whichever occurs first. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1
    date_rangeTime Frame:
    From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • TTR per RECIST 1.1 as assessed by the investigator
    TTR is defined as the time from the start of study treatment until the date of first documented complete or partial response (if confirmed) per RECIST 1.1 as assessed by the investigator. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1
    date_rangeTime Frame:
    From first participant enrolled until end of treatment or end of imaging active follow-up (up to approximately 3 years)
  • Overall survival (OS)
    Defined as the time from the start of study treatment to the date of death from any cause.
    date_rangeTime Frame:
    From start of study intervention until death from any cause, or end of study (up to approximately 3 years), whichever comes first
  • Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) per CTCAE v 5.0, categorized by severity, including number of participants who discontinue study treatment due to an AE
    From first administration of study intervention up to 30 days (+5 days) after the last dose of study intervention.
    date_rangeTime Frame:
    From first participant enrolled until up to 30 days after the last administration of study treatment
  • Time to deterioration in EORTC QLQ-C30 physical functioning domain score
    The EORTC QLQ-C30 is a multi-dimensional validated cancer-specific quality of life (QoL) questionnaire developed by the EORTC Study Group on QoL for use in international clinical trial settings. The EORTC QLQ-C30 will be used to evaluate the time to deterioration in the physical functioning domain score. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30
    date_rangeTime Frame:
    Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years)
  • Change from baseline in EORTC QLQ-C30 physical functioning domain score
    The EORTC QLQ-C30 is a multi-dimensional validated cancer-specific quality of life (QoL) questionnaire developed by the EORTC Study Group on QoL for use in international clinical trial settings. The EORTC QLQ-C30 will be used to evaluate the change from baseline in the physical functioning domain score. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30
    date_rangeTime Frame:
    Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years)
  • Change from baseline in EORTC QLQ-C30 global health status/quality of life (QoL)
    The EORTC QLQ-C30 is a multi-dimensional validated cancer-specific quality of life (QoL) questionnaire developed by the EORTC Study Group on QoL for use in international clinical trial settings. The EORTC QLQ-C30 will be used to evaluate the change from baseline in global health status/QoL. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30
    date_rangeTime Frame:
    Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years)

Trial design

A Phase 2 open-label basket study to evaluate the efficacy and safety of orally administered reversible tyrosine kinase inhibitor BAY 2927088 in participants with metastatic or unresectable solid tumors with HER2-activating mutations
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
1