Recruiting

Advanced solid tumors, HER2 mutation

Bayer Identifier:

22752

ClinicalTrials.gov Identifier:

NCT06760819

EudraCT Number:

Not Available

EU CT Number:

2024-517419-62-00

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)

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 (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.

Key Participants Requirements

Sex

All

Age

18 - N/A (No Limit)

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

Trial summary

Enrollment Goal

111

Trial Dates

February 2025 - October 2029

Phase

Phase II

Could I Receive a placebo

Products

Sevabertinib, BAY 2927088

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Withdrawn	Gynecology Oncology clinic at UW Medical Center - Montlake	Seattle, 98195, United States
Not Yet Recruiting	UW Health Carbone Cancer Center	Madison, 53792, United States
Recruiting	The University of Texas MD Anderson Cancer Center - Texas Medical Center	Houston, 77030, United States
Recruiting	City of Hope - Duarte Cancer Center	Duarte, 91010, United States
Recruiting	Dana-Farber Cancer Institute - Oncology Department	Boston, 02215, United States
Recruiting	SCRI Oncology Partners	Nashville, 37203, United States
Withdrawn	Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit	Detroit, 48202, United States
Not Yet Recruiting	Profound Research -OMG - TriAtria Cancer Center	Farmington Hills, 48334, United States
Recruiting	Florida Cancer Specialists & Research Institute - Fort Myers Cancer Center - Gladiolus	Fort Myers, 33908, United States
Recruiting	Cleveland Clinic - Oncology Department	Cleveland, 44195, United States
Not Yet Recruiting	UAB O'Neal Comprehensive Cancer Center - The Kirklin Clinic of UAB Hospital	Birmingham, 35233, United States
Recruiting	Institut Gustave Roussy - Departement d’Innovation Therapeutique et d’Essais Precoces (DITEP)	Villejuif, 94805, France
Not Yet Recruiting	Centre Oscar Lambret - Service Oncologie	Lille, 59000, France
Not Yet Recruiting	ICM - Institut du Cancer de Montpellier - Val d'Aurelle - CIPP	Montpellier, 34298, France
Recruiting	Centre Hospitalier Lyon Sud - Service oncologie medicale	Pierre‑Bénite, 69310, France
Recruiting	Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale	Bordeaux, 33000, France
Recruiting	CHU Brest - Hopital La Cavale Blanche - service oncologie medicale	Brest, 29200, France
Recruiting	Hokkaido University Hospital	Sapporo, 060-8648, Japan
Recruiting	Aichi Cancer Center Hospital	Nagoya, 464-8681, Japan
Recruiting	The Cancer Institute Hospital of JFCR	Koto-ku, 135-8550, Japan
Recruiting	Kindai University Hospital	Sakai, 590-0197, Japan
Recruiting	National Cancer Center Hospital	Chuo-ku, 104-0045, Japan
Recruiting	National Cancer Center Hospital East (NCCHE) - Kashiwa Campus	Kashiwa, 277-8577, Japan
Not Yet Recruiting	Azienda USL IRCCS di Reggio Emilia_Arcispedale Santa Maria Nuova - S.C. Oncologia Provinciale	Reggio Emilia, 42123, Italy
Recruiting	Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1	Milano, 20133, Italy
Recruiting	Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica	Roma, 00168, Italy
Not Yet Recruiting	Istituto Europeo di Oncologia s.r.l - Ginecologia Oncologica Medica	Milano, 20141, Italy
Recruiting	Institut Catala D'oncologia \| Hospitalet \| Oncologia	L'Hospitalet de Llobregat, 08908, Spain
Not Yet Recruiting	Clinica Universidad De Navarra \| Madrid \| Oncologia	Madrid, 28027, Spain
Recruiting	Hospital Universitario Fundacion Jimenez Diaz \| Oncologia Medica	Madrid, 28040, Spain
Recruiting	Hospital Universitari Vall D Hebron \| Oncologia Medica	Barcelona, 08035, Spain
Not Yet Recruiting	Instituto Oncologico Dr. Rosell S.L. \| Oncologia	Barcelona, 08028, Spain
Recruiting	Princess Margaret Cancer Centre \| Medical Oncology and Hematology	Toronto, M5G 2C4, Canada
Completed	Research Institute of the McGill University Health Centre \| Women Health's Research Unit	Montreal, H4A 3J1, Canada
Not Yet Recruiting	Queen Elizabeth II Health Sciences Centre \| Oncology	Halifax, B3H 2Y9, Canada
Not Yet Recruiting	Aarhus University Hospital \| Oncology Department - Clinical Research Unit	Aarhus N, 8200, Denmark
Recruiting	Odense University Hospital \| Svendborg Sygehus - Oncology Department	Odense, 5000, Denmark
Recruiting	Rigshospitalet Copenhagen University Hospital \| Oncology Department	Copenhagen, 2100, Denmark
Not Yet Recruiting	ICON Cancer Centre - Southport	Southport, 4215, Australia
Recruiting	NSW Health – Blacktown Hospital	Blacktown, 2148, Australia
Recruiting	Macquarie University Hospital - Oncology Department	Sydney, 2109, Australia
Recruiting	Beijing Cancer Hospital - Oncology Department	Beijing, 100142, China
Not Yet Recruiting	Hunan Cancer Hospital - Oncology Department	Changsha, 410013, China
Recruiting	Zhongshan Hospital, Fudan University	Shanghai, 200032, China
Not Yet Recruiting	Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department	Hangzhou, 310016, China
Recruiting	Fudan University Shanghai Cancer Center - Oncology Department	Shanghai, 200000, China
Recruiting	Peking University First Hospital - Oncology Department	Beijing, 100034, China
Recruiting	Asan Medical Center \| Oncology	Seoul, 05505, South Korea
Recruiting	Samsung Medical Center \| Oncology	Seoul, 06351, South Korea
Active, not recruiting	Seoul National University Hospital \| Oncology	Jongno -Gu, 03080, South Korea
Recruiting	Severance Hospital \| Oncology	Seoul, 03722, South Korea
Not Yet Recruiting	Inselspital Bern - Universitätsklinik für Medizinische Onkologie	Bern, 3010, Switzerland
Not Yet Recruiting	Hopitaux Universitaires de Geneve - Oncology Department	Geneva, 1205, Switzerland
Recruiting	UniversitätsSpital Zürich (USZ) - Klinik für Medizinische Onkologie und Hämatologie	Zürich, 8091, Switzerland

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)
Time 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)
Time 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)
Time 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
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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
Time 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
Time 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
Time 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.
Time 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 after the last dose of study intervention.
Time 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
Time 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
Time 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
Time 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

Open Label

Assignment

Single Group

Trial Arms

Additional Information

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