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)

Official title

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

Overview

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.

Interventions

• Drug BAY2927088
  tablet, oral

Primary outcome measures

• Objective Response Rate (ORR) per RECIST 1.1 as assessed by 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 measures (12)

• Duration of response (DOR) per RECIST 1.1 as assessed by 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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [Time frame: From start of study intervention until death from any cause, or end of study (up to approximately 3 years), whichever comes first]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• UAB O'Neal Comprehensive Cancer Center - The Kirklin Clinic of UAB Hospital — Birmingham
• City of Hope - Duarte Cancer Center — Duarte
• Florida Cancer Specialists & Research Institute - Fort Myers Cancer Center - Gladiolus — Fort Myers
• Dana-Farber Cancer Institute - Oncology Department — Boston
• Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit — Detroit
• Profound Research -OMG - TriAtria Cancer Center — Farmington Hills
• Cleveland Clinic - Oncology Department — Cleveland
• SCRI Oncology Partners — Nashville
• … and 3 more centers

China · 6 centers

• Peking University First Hospital - Oncology Department — Beijing
• Beijing Cancer Hospital - Oncology Department — Beijing
• Hunan Cancer Hospital - Oncology Department — Changsha
• Fudan University Shanghai Cancer Center - Oncology Department — Shanghai
• Zhongshan Hospital, Fudan University — Shanghai
• Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department — Hangzhou

France · 6 centers

• Centre Hospitalier Lyon Sud - Service oncologie medicale — Pierre-Bénite
• CHU Brest - Hopital La Cavale Blanche - service oncologie medicale — Brest
• Centre Oscar Lambret - Service Oncologie — Lille
• Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale — Bordeaux
• ICM - Institut du Cancer de Montpellier - Val d'Aurelle - CIPP — Montpellier
• Institut Gustave Roussy - Departement d'Innovation Therapeutique et d'Essais Precoces (DIT — Villejuif

Japan · 6 centers

• Aichi Cancer Center Hospital — Nagoya
• National Cancer Center Hospital East (NCCHE) - Kashiwa Campus — Kashiwa
• Hokkaido University Hospital — Sapporo
• Kindai University Hospital — Sakai
• National Cancer Center Hospital — Chuo-ku
• The Cancer Institute Hospital of JFCR — Koto-ku

Spain · 5 centers

• Institut Catala D'oncologia | Hospitalet | Oncologia — L'Hospitalet de Llobregat
• Clinica Universidad De Navarra | Madrid | Oncologia — Madrid
• Instituto Oncologico Dr. Rosell S.L. | Oncologia — Barcelona
• Hospital Universitari Vall D Hebron | Oncologia Medica — Barcelona
• Hospital Universitario Fundacion Jimenez Diaz | Oncologia Medica — Madrid

Italy · 4 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1 — Milan
• Istituto Europeo di Oncologia s.r.l - Ginecologia Oncologica Medica — Milan
• Azienda USL IRCCS di Reggio Emilia_Arcispedale Santa Maria Nuova - S.C. Oncologia Provinci — Reggio Emilia
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica — Roma

South Korea · 4 centers

• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System - Oncology Department — Seoul
• Asan Medical Center | Oncology — Seoul
• Samsung Medical Center - Oncology Department — Seoul

Australia · 3 centers

• NSW Health - Blacktown Hospital — Blacktown
• Macquarie University Hospital - Oncology Department — Sydney
• ICON Cancer Centre - Southport — Southport

Canada · 3 centers

• Queen Elizabeth II Health Sciences Centre | Oncology — Halifax
• Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncolo — Toronto
• McGill University Health Centre - Glen Site - Women Health's Research Unit — Montreal

Denmark · 3 centers

• Rigshospitalet Copenhagen University Hospital | Oncology Department — Copenhagen
• Aarhus University Hospital | Oncology Department - Clinical Research Unit — Aarhus N
• Odense University Hospital | Svendborg Sygehus - Oncology Department — Odense

Switzerland · 3 centers

• Inselspital Bern - Universitätsklinik für Medizinische Onkologie — Bern
• Hopitaux Universitaires de Geneve - Oncology Department — Geneva
• UniversitätsSpital Zürich (USZ) - Klinik für Medizinische Onkologie und Hämatologie — Zurich

Identifiers

NCT: NCT06760819 · 22752 · 2024-517419-62-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗