Clinical trial • Phase I/II • Oncology
ZONGERTINIB for Metastatic gastric adenocarcinoma | Gastroesophageal junction adenocarcinoma | Esophageal adenocarcinoma | Metastatic breast cancer
Phase I/II trial of ZONGERTINIB for Metastatic gastric adenocarcinoma | Gastroesophageal junction adenocarcinoma | Esophageal adenocarcinoma | Metastatic…
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Metastatic gastric adenocarcinoma | Gastroesophageal junction adenocarcinoma | Esophageal adenocarcinoma | Metastatic breast cancer
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule | Monoclonal antibody | ADC
Key dates
- Initial CTIS Submission Date
- 07-03-2024
- First CTIS Authorization Date
- 10-06-2024
Trial design
Randomised, open-label, multiple interventional arms described: zongertinib (bi 1810631) monotherapy and zongertinib in combination with other agents (t-dm1, t-dxd, capecitabine + trastuzumab, trastuzumab). no placebo or separate active comparator arm with dose/schedule specified in the available part i/ii information.-controlled, adaptive Phase I/II trial across 44 sites in Belgium, Italy, Spain and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Multiple interventional arms described: zongertinib (BI 1810631) monotherapy and zongertinib in combination with other agents (T-DM1, T-DXd, capecitabine + trastuzumab, trastuzumab). No placebo or separate active comparator arm with dose/schedule specified in the available Part I/II information.
- Adaptive
- True, dose-escalation design uses Bayesian Logistic Regression Model (BLRM) with overdose control (EWOC) and a Dose Escalation Committee (DEC) to determine MTDs; MTD evaluation period defined as first 21 days of cycle 1; escalation with overdose control and predefined risk threshold (<25% risk of true DLT rate ≥33%) described.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 452
Eligibility
Recruits 452 Vulnerable population not selected; participants must be ≥18 years of age or over the legal age of consent in their country. Informed consent is to be obtained from the participant. No paediatric assent/parental consent provisions are described in the available Part I/II information..
- Vulnerable Population
- Vulnerable population not selected; participants must be ≥18 years of age or over the legal age of consent in their country. Informed consent is to be obtained from the participant. No paediatric assent/parental consent provisions are described in the available Part I/II information.
Inclusion criteria
- {"criterion_text":"- Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF)\n- Documented HER2+ mBC or mGEAC\n- For dose optimization (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue\n- Documented investigator assessed progression\n- Presence of at least one measurable lesion according to RECIST 1.1\n- Eastern Cooperative Oncology Group (ECOG) score of 0 or 1\n- Adequate organ function based on laboratory values"}
Exclusion criteria
- {"criterion_text":"- Mean resting corrected QT interval (QTcF) >470 msec.\n- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, personal or family history of long QT syndrome or unexplained sudden death under 40 years-of-age\n- Ejection fraction <50% or the lower limit of normal of the institutional standard within 28 days prior to randomization\n- History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Dose escalation (Phase Ib) Occurrence of DLTs in the MTD evaluation period. The MTD evaluation period is defined as the first 21 days of the first treatment cycle","definition_or_measurement_approach":"Occurrence of dose-limiting toxicities (DLTs) assessed during the MTD evaluation period defined as the first 21 days of the first treatment cycle; MTD determined by Dose Escalation Committee (DEC) using Bayesian Logistic Regression Model with overdose control (EWOC)."}
- {"endpoint_text":"- Dose optimization (Phase II) Objective response (OR) defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation as assessed by investigator review","definition_or_measurement_approach":"Objective response (OR) per RECIST version 1.1 assessed by investigator review; best overall confirmed CR or PR from treatment start until earliest of progression, death, last evaluable assessment before subsequent therapy, or treatment discontinuation."}
Secondary endpoints
- {"endpoint_text":"- Dose escalation (Phase Ib) OR, as described above","definition_or_measurement_approach":"Objective response as described in the primary endpoint (RECIST v1.1, investigator-assessed)."}
- {"endpoint_text":"- Occurrence of DLTs during the entire treatment period","definition_or_measurement_approach":"Occurrence of dose-limiting toxicities (DLTs) monitored throughout treatment period."}
- {"endpoint_text":"- Intensive PK sampling: The following PK parameters of zongertinib when given in combination will be evaluated if feasible: o Cmax (SS): maximum measured concentration (at steady state) o AUC0-4h,ss : area under the concentration-time curve over the time interval from 0 to 4h at steady state o AUC0tz,ss: area under the concentration-time curve over the time interval from 0 to the last quantifiable data point at steady state","definition_or_measurement_approach":"Pharmacokinetic parameters measured by intensive sampling when feasible: Cmax (steady state), AUC0-4h,ss, AUC0-tz,ss as defined."}
- {"endpoint_text":"- Dose optimization (Phase II) o Progression-free survival (PFS), defined as the time from treatment start until the earliest date of tumor progression according RECIST 1.1 based on investigator review or death from any cause, whichever occurs first","definition_or_measurement_approach":"PFS per RECIST 1.1 assessed by investigator review; time from treatment start to earliest of tumor progression or death."}
- {"endpoint_text":"- Disease control (DC) defined as best overall response of CR or PR or stable disease (SD) where best overall response is defined according to RECIST 1.1 from first treatment administration until the earliest of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation, as assessed by investigator review","definition_or_measurement_approach":"Disease control per RECIST 1.1 (best overall response CR, PR or SD) from first treatment until earliest of progression, death, last evaluable assessment before subsequent therapy, or treatment discontinuation."}
- {"endpoint_text":"- Occurrence of treatment-emergent AEs (TEAEs) \"redacted for CCI\"","definition_or_measurement_approach":"Occurrence of treatment-emergent adverse events (TEAEs); additional details redacted in source."}
- {"endpoint_text":"- Sparse PK sampling: The following PK parameters of zongertinib 1 when given as monotherapy or in combination will be evaluated if feasible: o Cmax (ss): maximum measured concentration (at steady state) o AUC0 tz, ss: area under the concentration-time curve over the time interval from 0 to the last quantifiable data point at steady state","definition_or_measurement_approach":"Pharmacokinetic parameters from sparse sampling when feasible: Cmax (ss), AUC0-tz (ss)."}
- {"endpoint_text":"- PROs: PRO-CTCAE (Mouth/throat sores, Taste changes, Decreased appetite, Nausea, Vomiting, Constipation, Diarrhoea, Shortness of breath, Cough, Rash, Skin dryness, Hair loss, Itching, Numbness & Tingling, Fatigue, Nosebleed, Headache); EORTC IL46 (1 item, overall side effect impact); EORTC IL19 (5 items, physical functioning scale of EORTC QLQ-C30). The time frame is from first administration until an individual patient’s end of treatment (EOT).","definition_or_measurement_approach":"Patient-reported outcomes using PRO-CTCAE, EORTC IL46 and EORTC IL19; timeframe from first administration to patient's end of treatment (EOT)."}
Recruitment
- Planned Sample Size
- 452
- Recruitment Window Months
- 50
- Consent Approach
- Informed consent obtained from the participant (participants must be ≥18 years or over the legal age of consent in their country). Subject information and ICF documents available in multiple language versions (EN, FR, NL, IT, ES) including main Part A and Part B, biobanking, pregnancy/partner documents; consent forms are site-specific versions (country-specific ICFs listed).
Methods
- Physician referral (physician-facing physician referral brochure documents listed)
- Dr-to-Patient letters (K2 Dr-to-Patient Letter documents listed; target: potential patients via treating physicians)
- Patient flyers / brochures (K2 Patient Flyer and Patient Brochure documents listed; target: patients)
- Site-level recruitment arrangements (K1_Recruitment Arrangements documents present)
Geography
- Total Number Of Sites
- 44
- Total Number Of Participants
- 199
Belgium
- Earliest CTIS Part Ii Submission Date
- 02-05-2024
- Latest Decision Or Authorization Date
- 02-10-2025
- Processing Time Days
- 518
- Number Of Sites
- 5
- Number Of Participants
- 25
Sites
- Site Name
- Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
- Department Name
- Oncology
- Contact Person Name
- Claire Quaghebeur
- Contact Person Email
- claire.quaghebeur@uclouvain.be
- Site Name
- Antwerp University Hospital
- Department Name
- Medical Oncology
- Contact Person Name
- Hans Prenen
- Contact Person Email
- hans.prenen@uza.be
- Site Name
- UZ Leuven
- Department Name
- Medical Oncology
- Contact Person Name
- Hans Wildiers
- Contact Person Email
- Hans.wildiers@uzleuven.be
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Medical Oncology
- Contact Person Name
- Cedric Van Marcke de Lummen
- Contact Person Email
- cedric.vanmarcke@saintluc.uclouvain.be
- Site Name
- Hopital De Libramont
- Department Name
- Oncology
- Contact Person Name
- Frédéric Forget
- Contact Person Email
- frederic.forget@vivalia.be
Italy
- Earliest CTIS Part Ii Submission Date
- 22-01-2024
- Latest Decision Or Authorization Date
- 22-09-2025
- Processing Time Days
- 578
- Number Of Sites
- 8
- Number Of Participants
- 55
Sites
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- U.O. Oncologia Medica
- Contact Person Name
- Gianluca Del Conte
- Contact Person Email
- delconte.gianluca@hsr.it
- Site Name
- Humanitas Istituto Clinico Catanese S.p.A.
- Department Name
- U.O. Oncologia Medica
- Contact Person Name
- Michele Caruso
- Contact Person Email
- michele.caruso@humanitascatania.it
- Site Name
- Istituto Europeo Di Oncologia S.r.l.
- Department Name
- Div. Sviluppo Nuovi Farmaci per Terapie Innovative
- Contact Person Name
- Giuseppe Curigliano
- Contact Person Email
- giuseppe.curigliano@ieo.it
- Site Name
- Humanitas Research Hospital
- Department Name
- O.U. Oncologia Medica ed Ematologia
- Contact Person Name
- Matteo Simonelli
- Contact Person Email
- matteo.simonelli@cancercenter.humanitas.it
- Site Name
- Istituto Di Candiolo Fondazione Del Piemonte Per L'Oncologia IRCCS
- Department Name
- Oncologia Medica
- Contact Person Name
- Virginia Quarà
- Contact Person Email
- virginia.quara@ircc.it
- Site Name
- Azienda Ospedaliero Universitaria Delle Marche
- Department Name
- Clinica Oncologica
- Contact Person Name
- Rossana Berardi
- Contact Person Email
- rossana.berardi@ospedaliriuniti.marche.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- Sperimentazioni Cliniche
- Contact Person Name
- Adriano Gravina
- Contact Person Email
- a.gravina@istitutotumori.na.it
- Site Name
- Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
- Department Name
- Oncologia Medica
- Contact Person Name
- Michela Palleschi
- Contact Person Email
- michela.palleschi@irst.emr.it
Spain
- Earliest CTIS Part Ii Submission Date
- 29-04-2024
- Latest Decision Or Authorization Date
- 26-11-2025
- Processing Time Days
- 576
- Number Of Sites
- 15
- Number Of Participants
- 66
Sites
- Site Name
- Complexo Hospitalario Universitario A Coruna
- Department Name
- Oncology
- Contact Person Name
- Silvia Antolín Novoa
- Contact Person Email
- silvia.antolin.novoa@sergas.es
- Site Name
- Hospital Del Mar
- Department Name
- Oncology
- Contact Person Name
- María Martínez García
- Contact Person Email
- mariamartinezgarcia@hmar.cat
- Site Name
- Hospital Universitario La Paz
- Department Name
- Oncology
- Contact Person Name
- Ana Belén Custodio Carretero
- Contact Person Email
- anabcuestodio@gmail.com
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Department of Oncology
- Contact Person Name
- Daniel Acosta Eyzaguirre
- Contact Person Email
- dacosta@vhio.net
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Oncology
- Contact Person Name
- Ivan Manuel Victoria Ruiz
- Contact Person Email
- IVICTORI@recerca.clinic.cat
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Oncology
- Contact Person Name
- José Ángel García Saénz
- Contact Person Email
- jgsaenz@salud.madrid.org
- Site Name
- Institut Catala D'oncologia
- Department Name
- Trucco
- Contact Person Name
- Agostina Stradella
- Contact Person Email
- aestradella@iconcologia.net
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz
- Department Name
- Oncology
- Contact Person Name
- Bernard Doger de Speville
- Contact Person Email
- bernard.doger@startmadrid.com
- Site Name
- Fundacion Instituto Valenciano De Oncologia
- Department Name
- Oncology
- Contact Person Name
- Angel Luis Guerrero Zotano
- Contact Person Email
- AGUERRERO@FIVO.ORG
- Site Name
- Clinica Universidad De Navarra (Madrid)
- Department Name
- Oncology
- Contact Person Name
- Ignacio Matos García
- Contact Person Email
- imatos@unav.es
- Site Name
- Hospital Universitario Hm Sanchinarro
- Department Name
- Oncology, Clinical Trials Phase I START Madrid-CIOCC Centro Integral Oncologico Clara Campal
- Contact Person Name
- Ramón Yarza Barrio
- Contact Person Email
- ramon.yarza@startmadrid.com
- Site Name
- Hospital Universitario Virgen De La Macarena
- Department Name
- Oncology
- Contact Person Name
- Luis De la Cruz Merino
- Contact Person Email
- ldelacruzmerino@gmail.com
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Oncology
- Contact Person Name
- Sara López-Tarruella Cobo
- Contact Person Email
- slopeztarruella@gmail.com
- Site Name
- Clinica Universidad De Navarra (Pamplona)
- Department Name
- Oncology
- Contact Person Name
- Ignacio Matos García
- Contact Person Email
- imatos@unav.es
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Oncology
- Contact Person Name
- Jon Zugazagoitia Fraile
- Contact Person Email
- j.zugazagoitia.imas12@h12o.es
France
- Earliest CTIS Part Ii Submission Date
- 01-12-2025
- Latest Decision Or Authorization Date
- 13-01-2026
- Processing Time Days
- 43
- Number Of Sites
- 11
- Number Of Participants
- 33
Sites
- Site Name
- Institut Paoli Calmettes
- Department Name
- Oncologie médicale
- Contact Person Name
- Arthur GÉRAUD-CRÉMIEUX
- Contact Person Email
- geraudcremieuxa@ipc.unicancer.fr
- Site Name
- Centre Francois Baclesse
- Department Name
- Maladies digestives
- Contact Person Name
- Mélanie DOS SANTOS
- Contact Person Email
- m.dossantos@baclesse.unicancer.fr
- Site Name
- Centre Georges Francois Leclerc
- Department Name
- Oncologie médicale
- Contact Person Name
- François GHIRINGHELLI
- Contact Person Email
- fghiringhelli@cgfl.fr
- Site Name
- Centre Leon Berard
- Department Name
- Oncologie médicale
- Contact Person Name
- Hélène VANACKER
- Contact Person Email
- helene.vanacker@lyon.unicancer.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Oncologie médicale
- Contact Person Name
- Joseph GLIGOROV
- Contact Person Email
- joseph.gligorov@aphp.fr
- Site Name
- Oncopole Claudius Regaud
- Department Name
- Oncologie
- Contact Person Name
- Florence DALENC
- Contact Person Email
- dalenc.florence@iuct-oncopole.fr
- Site Name
- Institut De Cancerologie Strasbourg Europe
- Department Name
- Oncologie médicale
- Contact Person Name
- Laura SOMME
- Contact Person Email
- l.bender@icans.eu
- Site Name
- Institut Gustave Roussy
- Department Name
- Service de Médecine
- Contact Person Name
- Barbara PISTILLI
- Contact Person Email
- barbara.pistilli@gustaveroussy.fr
- Site Name
- Centre De Lutte Contre Le Cancer Eugene Marquis
- Department Name
- Oncologie
- Contact Person Name
- Thibault DE LA MOTTE ROUGE
- Contact Person Email
- t.delamotterouge@rennes.unicancer.fr
- Site Name
- Institut Bergonie
- Department Name
- Oncologie médicale
- Contact Person Name
- Antoine ITALIANO
- Contact Person Email
- a.italiano@bordeaux.unicancer.fr
- Site Name
- Institut De Cancerologie De L Ouest
- Department Name
- Oncologie médicale
- Contact Person Name
- Jean-Sebastien FRENEL
- Contact Person Email
- jean-sebastien.frenel@ico.unicancer.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 08-12-2025
- Latest Decision Or Authorization Date
- 07-01-2026
- Processing Time Days
- 30
- Number Of Sites
- 5
- Number Of Participants
- 20
Sites
- Site Name
- Universitaetsklinikum Erlangen AöR
- Department Name
- Frauenklinik
- Contact Person Name
- Peter Fasching
- Contact Person Email
- peter.fasching.studien@uk-erlangen.de
- Site Name
- Universitaetsklinikum Mannheim GmbH
- Department Name
- Medizinische Klinik
- Contact Person Name
- Frederik Marme
- Contact Person Email
- Frederik.marme@umm.de
- Site Name
- Asklepios Kliniken Hamburg GmbH
- Department Name
- Onkologie und Palliativmedizin mit Sektionen Hämatologie und Rheumatologie
- Contact Person Name
- Dirk Arnold
- Contact Person Email
- d.arnold@asklepios.com
- Site Name
- Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
- Department Name
- Klinik und Poliklinik f. Frauenheilkunde
- Contact Person Name
- Pauline Wimberger
- Contact Person Email
- pauline.wimberger@ukdd.de
- Site Name
- KEM I Evang. Kliniken Essen-Mitte gGmbH
- Department Name
- Klinik für Senologie/ Interdisziplinäres Brustzentrum
- Contact Person Name
- Sherko Kümmel
- Contact Person Email
- s.kuemmel@kem-med.com
Sponsor
Primary sponsor
- Full Name
- Boehringer Ingelheim International GmbH
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Germany
Contract research organisations
- Name
- PPD Development LP
- Responsibilities
- Sponsor duties code: 4 (operational support)
- Name
- IQVIA Limited
- Responsibilities
- Responsibilities include eCOA and translation of documents (sponsorDuties entries include codes 1,12,15 and value 'eCOA, translation of documents'; also codes 2 and 5 listed).
- Name
- Labcorp Early Development Laboratories Limited
- Responsibilities
- Central laboratory services (sponsorDuties code: 4)
- Name
- Bioclinica Inc.
- Responsibilities
- Imaging services (sponsorDuties code: 15, value 'imaging')
Third parties
- {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Boehringer Ingelheim Pharma GmbH & Co. KG","duties_or_roles":"sponsorDuties codes: 15 (Biobanking Biopsy)","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1,12,15 (eCOA, translation of documents),2,5","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"MENAL Gesellschaft fuer medizinische und naturwissenschaftliche Laboranalytik mbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"AG Mednet Inc.","duties_or_roles":"sponsorDuties codes: 15 (Adjudication tool to capture relevant clinical data)","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"sponsorDuties codes: 15 (imaging)","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: 15 (Medical Imaging Services)","organisation_type":"Pharmaceutical company"}
- {"country":"Austria","full_name":"Cbmed GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
Investigational products
- Investigational Product Name
- BI 1810631
- Active Substance
- ZONGERTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- Investigational medicinal product (no marketing authorisation listed in Part I product info)
- Combination Treatment
- Yes
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