A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) 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) (panSOHO)

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

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 (sevabertinib) 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 breast, 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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors; HER2 Mutation
• Intervention / Treatment: Drug: BAY2927088

• Study Type: Interventional
• Enrollment (Estimated): 111
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Bayer Clinical Trials Contact; Phone Number: (+)1-888-84 22937; Email: clinical-trials-contact@bayer.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Recruiting
      • NSW Health - Blacktown Hospital
    • Sydney, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University Hospital - Oncology Department
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • ICON Cancer Centre - Southport
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Recruiting
      • Queen Elizabeth II Health Sciences Centre | Oncology
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and Hematology
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre - Glen Site - Women Health's Research Unit
• China
  • Shanghai, China, 200000
    • Recruiting
    • Fudan University Shanghai Cancer Center - Oncology Department
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital - Oncology Department
    • Beijing, Beijing Municipality, China, 100034
      • Recruiting
      • Peking University First Hospital - Oncology Department
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital - Oncology Department
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zhongshan Hospital, Fudan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Recruiting
      • Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department
• Denmark
  • Capital Region
    • Copenhagen, Capital Region, Denmark, 2100
      • Recruiting
      • Rigshospitalet Copenhagen University Hospital | Oncology Department
  • Central Jutland
    • Aarhus N, Central Jutland, Denmark, 8200
      • Recruiting
      • Aarhus University Hospital | Oncology Department - Clinical Research Unit
  • Region Syddanmark
    • Odense, Region Syddanmark, Denmark, 5000
      • Recruiting
      • Odense University Hospital | Svendborg Sygehus - Oncology Department
• France
  • Auvergne-Rhône-Alpes
    • Pierre-Bénite, Auvergne-Rhône-Alpes, France, 69310
      • Recruiting
      • Centre Hospitalier Lyon Sud - Service oncologie medicale
  • Brittany Region
    • Brest, Brittany Region, France, 29200
      • Recruiting
      • CHU Brest - Hopital La Cavale Blanche - service oncologie medicale
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59000
      • Recruiting
      • Centre Oscar Lambret - Service Oncologie
  • New Aquitaine
    • Bordeaux, New Aquitaine, France, 33000
      • Recruiting
      • Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale
  • Occitanie
    • Montpellier, Occitanie, France, 34298
      • Recruiting
      • ICM - Institut du Cancer de Montpellier - Val d'Aurelle - CIPP
  • Île-de-France Region
    • Villejuif, Île-de-France Region, France, 94805
      • Recruiting
      • Institut Gustave Roussy - Departement d'Innovation Therapeutique et d'Essais Precoces (DITEP)
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1
  • Milan, Italy, 20141
    • Recruiting
    • Istituto Europeo di Oncologia s.r.l - Ginecologia Oncologica Medica
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • Azienda USL IRCCS di Reggio Emilia_Arcispedale Santa Maria Nuova - S.C. Oncologia Provinciale
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East (NCCHE) - Kashiwa Campus
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Recruiting
      • Hokkaido University Hospital
  • Osaka
    • Sakai, Osaka, Japan, 590-0197
      • Recruiting
      • Kindai University Hospital
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
    • Koto-ku, Tokyo, Japan, 135-8550
      • Recruiting
      • The Cancer Institute Hospital Of JFCR
• South Korea
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center - Oncology Department
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 3080
      • Recruiting
      • Seoul National University Hospital
    • Seoul, Seoul Teugbyeolsi, South Korea, 03722
      • Recruiting
      • Severance Hospital, Yonsei University Health System - Oncology Department
    • Seoul, Seoul Teugbyeolsi, South Korea, 05505
      • Recruiting
      • Asan Medical Center | Oncology
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall D Hebron | Oncologia Medica
  • Barcelona, Spain, 08028
    • Recruiting
    • Instituto Oncologico Dr. Rosell S.L. | Oncologia
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz | Oncologia Medica
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Recruiting
      • Institut Catala D'oncologia | Hospitalet | Oncologia
  • Navarre
    • Madrid, Navarre, Spain, 28027
      • Recruiting
      • Clinica Universidad De Navarra | Madrid | Oncologia
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital Bern - Universitätsklinik für Medizinische Onkologie
  • Geneva, Switzerland, 1205
    • Recruiting
    • Hopitaux Universitaires de Geneve - Oncology Department
  • Zurich, Switzerland, 8091
    • Recruiting
    • Univestitätsspital Zürich (USZ)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • UAB O'Neal Comprehensive Cancer Center - The Kirklin Clinic of UAB Hospital
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope - Duarte Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Recruiting
      • Florida Cancer Specialists & Research Institute - Fort Myers Cancer Center - Gladiolus
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute - Oncology Department
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Withdrawn
      • Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Profound Research -OMG - TriAtria Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic - Oncology Department
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center - Texas Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • Withdrawn
      • Gynecology Oncology clinic at UW Medical Center - Montlake
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • UW Health Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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; breast 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BAY2927088; Adult participants with metastatic or unresectable solid tumors with HER-2 activating mutations including: colorectal, biliary tract, bladder, cervical, endometrial, breast, 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

Drug: BAY2927088; tablet, oral; Other Names: Sevabertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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 Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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	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.	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.	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.	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.	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.	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	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	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	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.	From start of study intervention until death from any cause, or end of study (up to approximately 3 years), whichever comes first
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	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	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	Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years)
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 after the last dose of study intervention.	From first participant enrolled until up to 30 days after the last administration of study treatment

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2025
• Primary Completion (Estimated): February 3, 2027
• Study Completion (Estimated): October 25, 2027

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 30, 2024
• First Posted (Actual): January 7, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Bladder cancer; Gastric cancer; Breast cancer; Ovarian Cancer; Pancreatic cancer; Sarcoma; Esophageal cancer; CRC; Cervical cancer; Endometrial cancer; GI cancer; GIST; Ampullary cancer; Gallbladder cancer; Urothelial cancer; Biliary tract cancer; Gastrointestinal cancer; Gastrointestinal stromal tumor; BTC; Salivary cancer; HER2 mutant cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Biliary Tract Diseases; Colonic Diseases; Esophageal Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Uterine Cervical Diseases; Uterine Neoplasms; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Urinary Bladder Diseases; Gallbladder Diseases; Skin and Connective Tissue Diseases; Stomach Neoplasms; Biliary Tract Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Gastrointestinal Neoplasms; Uterine Cervical Neoplasms; Sarcoma; Urinary Bladder Neoplasms; Endometrial Neoplasms; Gallbladder Neoplasms; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: 22752; 2024-517419-62-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No