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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)

Phase 2
Recruiting
Conditions
Advanced Solid Tumors
HER2 Mutation
Interventions
Registration Number
NCT06760819
Lead Sponsor
Bayer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
111
Inclusion Criteria
  • 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
Exclusion 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BAY2927088BAY2927088Adult participants with metastatic or unresectable solid tumors with HER-2 activating mutations including: colorectal, biliary tract, bladder, cervical, endometrial, and other solid tumor types. Participants will receive BAY2927088 20 mg BID until disease progression per RECICST 1.1, unacceptable toxicity, or until any other withdrawal criteria. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BID: twice a day
Primary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICRFrom 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

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)

Secondary Outcome Measures
NameTimeMethod
Duration of response (DOR) per RECIST 1.1 as assessed by BICRFrom 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 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)

Time to response (TTR) per RECIST 1.1 as assessed by BICRFrom first participant enrolled until end of treatment or end of imaging active follow-up (up to approximately 3 years)

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)

ORR per RECIST 1.1 as assessed by the investigatorFrom 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

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

Progression-free survival (PFS) per RECIST 1.1 as assessed by BICRFrom 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

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.

Disease control rate (DCR) per RECIST 1.1 as assessed by BICRFrom 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 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.

DCR ≥12 weeks per RECIST 1.1 as assessed by BICRFrom 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

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.

Disease control rate (DCR) per RECIST 1.1 as assessed by the investigatorFrom 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

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.

DCR ≥12 weeks per RECIST 1.1 as assessed by the investigatorFrom 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

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.

Progression-free survival (PFS) per RECIST 1.1 as assessed by the investigatorFrom 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

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

DOR per RECIST 1.1 as assessed by the investigatorFrom 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 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

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 AEFrom first participant enrolled until up to 30 days after the last administration of study treatment

From first administration of study intervention up to 30 days (+5 days) after the last dose of study intervention.

Change from baseline in EORTC QLQ-C30 global health status/quality of life (QoL)Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years)

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

TTR per RECIST 1.1 as assessed by the investigatorFrom first participant enrolled until end of treatment or end of imaging active follow-up (up to approximately 3 years)

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

Overall survival (OS)From start of study intervention until death from any cause, or end of study (up to approximately 3 years), whichever comes first

Defined as the time from the start of study treatment to the date of death from any cause.

Time to deterioration in EORTC QLQ-C30 physical functioning domain scoreBaseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years)

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

Change from baseline in EORTC QLQ-C30 physical functioning domain scoreBaseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years)

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

Trial Locations

Locations (51)

Hopitaux Universitaires de Geneve

🇨🇭

Genève, Switzerland

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

City of Hope - Duarte Cancer Center

🇺🇸

Duarte, California, United States

Florida Cancer Specialists & Research Institute - Fort Myers Cancer Center - Gladiolus

🇺🇸

Fort Myers, Florida, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit

🇺🇸

Detroit, Michigan, United States

Profound Research LLC

🇺🇸

Farmington Hills, Michigan, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

SCRI Oncology Partners

🇺🇸

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

University of Washington Medical Center (UWMC) - Montlake - Gynecology Oncology

🇺🇸

Seattle, Washington, United States

UW Health - UW Carbone Cancer Center - Medical Oncology Clinic

🇺🇸

Madison, Wisconsin, United States

Blacktown Cancer & Haematology Centre

🇦🇺

Blacktown, New South Wales, Australia

Macquarie University Hospital

🇦🇺

Sydney, New South Wales, Australia

ICON Cancer Centre - Southport

🇦🇺

Southport, Queensland, Australia

Queen Elizabeth II Health Sciences Centre - Victoria General Site

🇨🇦

Halifax, Nova Scotia, Canada

Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and Hematology

🇨🇦

Toronto, Ontario, Canada

McGill University Health Centre - Glen Site

🇨🇦

Montreal, Quebec, Canada

Peking University First Hospital

🇨🇳

Beijing, Beijing, China

Beijing Cancer Hospital

🇨🇳

Beijing, Beijing, China

Hunan Cancer Hospital

🇨🇳

Changsha, Hunan, China

Zhongshan Hospital, Fudan University

🇨🇳

Shanghai, Shanghai, China

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

🇨🇳

Hangzhou, Zhejiang, China

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai, China

Aarhus University Hospital

🇩🇰

Aarhus N, Denmark

Rigshospitalet - Kræftbehandling

🇩🇰

Copenhagen OE, Denmark

Odense University Hospital - Oncology Department

🇩🇰

Odense C, Denmark

Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale

🇫🇷

Bordeaux, France

CHU Brest - Hopital La Cavale Blanche - service oncologie medicale

🇫🇷

Brest, France

Centre Oscar Lambret - Service Oncologie

🇫🇷

Lille, France

Centre Hospitalier Lyon Sud - Service oncologie medicale

🇫🇷

Pierre-Benite, France

Institut Gustave Roussy - Departement d'Innovation Therapeutique et d'Essais Precoces (DITEP)

🇫🇷

Villejuif Cedex, France

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

🇮🇹

Milano, Italy

Azienda USL IRCCS di Reggio Emilia_Arcispedale Santa Maria Nuova - S.C. Oncologia Provinciale

🇮🇹

Reggio Emilia, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica

🇮🇹

Roma, Italy

Aichi Cancer Center Hospital

🇯🇵

Nagoya, Aichi, Japan

National Cancer Center Hospital East (NCCHE) - Kashiwa Campus

🇯🇵

Kashiwa, Chiba, Japan

Hokkaido University Hospital

🇯🇵

Sapporo, Hokkaido, Japan

Kindai University Hospital

🇯🇵

Osakasayama, Osaka, Japan

National Cancer Center Hospital

🇯🇵

Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital of JFCR

🇯🇵

Koto-ku, Tokyo, Japan

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Seoul Teugbyeolsi, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Seoul Teugbyeolsi, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Seoul Teugbyeolsi, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals

🇪🇸

L'Hospitalet de Llobregat, Barcelona, Spain

Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid

🇪🇸

Madrid, Navarra, Spain

Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)

🇪🇸

Barcelona, Spain

Fundacion Jimenez Diaz (Clinica de la Concepcion)

🇪🇸

Madrid, Spain

Inselspital Bern - Universitätsklinik für Medizinische Onkologie

🇨🇭

Bern, Switzerland

Univestitätsspital Zürich (USZ)

🇨🇭

Zürich, Switzerland

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