Clinical trial • Phase I/II | Phase II • Oncology
RILVEGOSTOMIG for HER2-expressing gastric cancer | HER2-expressing gastroesophageal junction (GEJ) adenocarcinoma | HER2-expressing esophageal adenocarcinoma
Phase I/II | Phase II trial of RILVEGOSTOMIG for HER2-expressing gastric cancer | HER2-expressing gastroesophageal junction (GEJ) adenocarcinoma | HER2-ex…
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- HER2-expressing gastric cancer | HER2-expressing gastroesophageal junction (GEJ) adenocarcinoma | HER2-expressing esophageal adenocarcinoma
- Trial Stage
- Phase I/II | Phase II
- Drug Modality
- Monoclonal antibody | Bispecific antibody | ADC | Small molecule
Key dates
- Initial CTIS Submission Date
- 25-09-2024
- First CTIS Authorization Date
- 08-10-2024
Trial design
open-label, cisplatin; trastuzumab (comparator arms listed; dose and schedule not specified in provided data)-controlled, adaptive Phase I/II | Phase II trial in Germany, Italy, Spain and others.
- Open Label
- Yes
- Comparator
- Cisplatin; Trastuzumab (comparator arms listed; dose and schedule not specified in provided data)
- Adaptive
- True, Part 1 is a dose-escalation design to assess safety/tolerability and determine the recommended Phase 2 dose (RP2D) or the highest protocol-defined dose; adaptive elements include assessment of dose-limiting toxicities (DLTs) and escalation to define RP2D.
- Biomarker Stratified
- True, biomarker: HER2 — strata: HER2-positive (IHC 3+ or IHC 2+/ISH+) | HER2-low (IHC 2+/ISH-negative or IHC 1+)
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 414
Eligibility
Recruits 414 Vulnerable population flag is selected in the registry. The protocol and provided documents include Subject Information Sheets and Informed Consent Forms for adult participants and specific ICFs for pregnant partners and optional genetic/future research. Participants must be ≥18 years and provide their own informed consent. No study-specific assent procedures for minors are provided in the available documents..
- Vulnerable Population
- Vulnerable population flag is selected in the registry. The protocol and provided documents include Subject Information Sheets and Informed Consent Forms for adult participants and specific ICFs for pregnant partners and optional genetic/future research. Participants must be ≥18 years and provide their own informed consent. No study-specific assent procedures for minors are provided in the available documents.
Inclusion criteria
- {"criterion_text":"- 1. Male and female participants must be at least 18 years of age. Other age restrictions mayapply as per local regulations\n- 2. Disease Characteristics: a/Locally advanced, unresectable, or metastatic disease based on most recent imaging b/For Parts 1, 2, 3a and 4a, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results c/For Parts 3b, 4b and Part 5 pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local tissue testing results\n- 3. For Part 1, progression on or after at least one prior trastuzumab-containing regimen For Part 2, 3, 4 and 5, previously untreated for unresectable or metastatic adenocarcinoma of the stomach/GEJ/ esophagus with HER2-positive (Part 2, Part 3 [Arm 3A] and Part 4[Arm 4A]) or HER2-low (Part 3 [Arm 3B] , Part 4 [Arm 4B] and Part 5) status.\n- 4. Has measurable target disease assessed by the Investigator based on RECIST version 1.1\n- 5. Has protocol-defined adequate bone marrow and organ function including cardiac, renal and hepatic function\n- 6. If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for female and 6 months (all treatment arms except Arm 2B) or 4 months (Arm 2B) for male patients"}
Exclusion criteria
- {"criterion_text":"- 1. Part 1 to 4: Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, active, chronic, or past hepatitis B infection, or hepatitis C infection. Part 5: Evidence of the following infections: Uncontrolled HIV infection, Active or uncontrolled hepatitis B (HBV) or hepatitis C (HCV) or active hepatitis A.\n- 2. Uncontrolled intercurrent illness.\n- 3. History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening.\n- 4. Lung-specific intercurrent clinically significant severe illnesses.\n- 5. Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.\n- 6. Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).\n- 7. Has spinal cord compression or clinically active central nervous system metastases.\n- 8. For Part 5: Any serious cardiac conditions, such as: Cardiomyopathy of any etiology or history of myocarditis, Heart failure, Uncontrolled hypertension, Unstable angina pectoris, Clinically significant coronary, carotid, or peripheral artery stenosis, Acute coronary syndrome/acute myocardial infarction etc."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0, dose-limiting toxicities (DLTs), and changes from baseline in laboratory parameters, vital signs, and electrocardiogram (ECG) results\n- Part 2, Part 3, Part 4 and Part 5: Endpoint assessed by Investigator per RECIST v1.1: Confirmed Objective Response Rate (ORR)","definition_or_measurement_approach":"Part 1: AEs/SAEs graded per NCI CTCAE v5.0; DLTs tracked; laboratory parameters, vital signs and ECG changes from baseline monitored. Part 2–5: Investigator-assessed confirmed Objective Response Rate (ORR) according to RECIST v1.1."}
Secondary endpoints
- {"endpoint_text":"- Part 1: Endpoints assessed by Investigator per RECIST v1.1: Confirmed Objective ResponseRate (ORR), Disease control rate (DCR), Duration of response (DoR), Progression-freesurvival (PFS), Overall survival (OS)\n- Part 2, Part 3, Part 4 and Part 5: Endpoints assessed by Investigator per RECISIT v1.1: Diseasecontrol rate (DCR), Duration of response (DoR), Progression-free survival (PFS), Overallsurvival (OS)\n- Part 2, Part 3, Part 4 and Part 5: Occurrence of adverse events (AEs) and serious adverse events(SAEs), dose-limiting toxicities (DLTs) and changes from baseline in laboratory parameters, vital signs, body weight and electrocardiogram (ECG) results\n- Part 2, Part 3, Part 4 and Part 5: -Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms; -Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab; -Serum concentrations of volrustomig and rilvegostomig in study arms including T-DXd incombination with volrustomig and T-DXd in combination with rilvegostomig,\n- -Presence of ADAs for T-DXd, durvalumab, volrustomig and rilvegostomig (in study arms including T-DXd and durvalumab T-DXd and volrustomig, and T-DXd and rilvegostomig, respectively) -Comparison of ORR, DCR, DoR, PFS, OS between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results","definition_or_measurement_approach":"Secondary endpoints are measured per RECIST v1.1 for tumor response metrics (ORR, DCR, DoR, PFS, OS). Safety endpoints use NCI CTCAE v5.0 grading. PK endpoints: serum concentrations of T-DXd, anti-HER2 antibody, MAAA-1181a, durvalumab, volrustomig, rilvegostomig. Immunogenicity: assessment of anti-drug antibodies (ADAs). Comparison analyses between local and central HER2 testing for response endpoints."}
Recruitment
- Planned Sample Size
- 414
- Recruitment Window Months
- 73
- Consent Approach
- Informed consent obtained from adult participants (minimum age 18). Subject Information Sheets and Informed Consent Forms are provided and available for country-specific use (documents available for DE, IT, ES, NL, PL and English versions). There are specific ICFs for pregnant partners and optional/genetic research; consent is provided by the participant. No assent procedures for minors are described in the available documents.
Methods
- Use of recruitment arrangements documents and patient-facing materials (posters and pamphlets) — country-specific recruitment arrangements files provided (Germany, Italy, Spain, Netherlands, Poland).
- Local site-based recruitment via participating hospitals/centres (contact details and responsible clinicians listed per site).
Geography
- Total Number Of Sites
- 30
- Total Number Of Participants
- 154
Germany
- Earliest CTIS Part Ii Submission Date
- 05-04-2024
- Latest Decision Or Authorization Date
- 09-10-2024
- Processing Time Days
- 187
- Number Of Sites
- 6
- Number Of Participants
- 27
Sites
- Site Name
- Universitaetsklinikum Frankfurt AöR
- Department Name
- Schwerpunkt GI Onkologie Medizinische Klinik 1
- Contact Person Name
- Jörg Trojan
- Contact Person Email
- trojan@em.uni-frankfurt.de
- Site Name
- Krankenhaus Nordwest GmbH
- Department Name
- Institut für Klinisch-Onkologische Forschung (IKF),UCT-Frankfurt
- Contact Person Name
- Salah-Eddin Al-Batran
- Contact Person Email
- albatran@khnw.de
- Site Name
- Universitaet Leipzig
- Department Name
- Universitäres Krebszentrum Leipzig (UCCL)
- Contact Person Name
- Florian Lordick
- Contact Person Email
- Florian.Lordick@medizin.uni-leipzig.de
- Site Name
- Universitaetsklinikum Mannheim GmbH
- Department Name
- Tagestherapiezentrum am ITM
- Contact Person Name
- Ralf-Dieter Hofheinz
- Contact Person Email
- ralf.hofheinz@umm.de
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- Klinik und Poliklinik für Innere Medizin III, Hämatologie
- Contact Person Name
- Sylvie Lorenzen
- Contact Person Email
- Sylvie.Lorenzen@mri.tum.de
- Site Name
- Haematologisch Onkologische Praxis Eppendorf
- Contact Person Name
- Alexander Stein
- Contact Person Email
- stein@hope-hamburg.de
Italy
- Earliest CTIS Part Ii Submission Date
- 05-04-2024
- Latest Decision Or Authorization Date
- 14-10-2024
- Processing Time Days
- 192
- Number Of Sites
- 7
- Number Of Participants
- 41
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Medical Oncology
- Contact Person Name
- Gennaro Daniele
- Contact Person Email
- gennaro.daniele@policlinicogemelli.it
- Site Name
- Istituto Oncologico Veneto
- Department Name
- Medical Oncology
- Contact Person Name
- Sara Lonardi
- Contact Person Email
- sara.lonardi@iov.veneto.it
- Site Name
- ASST Grande Ospedale Metropolitano Niguarda
- Department Name
- Oncology
- Contact Person Name
- Salvatore Siena
- Contact Person Email
- salvatore.siena@ospedaleniguarda.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- Medical Oncology
- Contact Person Name
- Adriano Gravina
- Contact Person Email
- a.gravina@istitutotumori.na.it
- Site Name
- Centro Ricerche Cliniche Di Verona S.r.l.
- Department Name
- Medical Oncology
- Contact Person Name
- Davide Melisi
- Contact Person Email
- davide.melisi@univr.it
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- Gastroenterological Medical Oncology
- Contact Person Name
- Filippo Pietrantonio
- Contact Person Email
- filippo.pietrantonio@istitutotumori.mi.it
- Site Name
- Centro Ricerche Cliniche Di Verona S.r.l. (duplicate entry in listing)
- Department Name
- Medical Oncology
- Contact Person Name
- Davide Melisi
- Contact Person Email
- davide.melisi@univr.it
Spain
- Earliest CTIS Part Ii Submission Date
- 05-04-2024
- Latest Decision Or Authorization Date
- 08-10-2024
- Processing Time Days
- 186
- Number Of Sites
- 6
- Number Of Participants
- 19
Sites
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Oncology
- Contact Person Name
- Maria Luisa Limon Miron
- Contact Person Email
- mluisalimon@gmail.com
- Site Name
- Hospital Universitario Marques De Valdecilla
- Department Name
- Oncology
- Contact Person Name
- Sara Lonardi
- Contact Person Email
- sara.lonardi@iov.veneto.it
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncology
- Contact Person Name
- Daniel Alejandro Acosta Eyzaguirre
- Contact Person Email
- dacosta@vhio.net
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Oncology
- Contact Person Name
- Aitana Calvo Ferrandiz
- Contact Person Email
- aitanacalvo@hotmail.com
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Oncology
- Contact Person Name
- Federico Longo Munoz
- Contact Person Email
- fedelongomunoz@hotmail.com
- Site Name
- Hospital Universitari Vall D Hebron (duplicate/other department)
- Department Name
- Oncology
- Contact Person Name
- Daniel Alejandro Acosta Eyzaguirre
- Contact Person Email
- dacosta@vhio.net
Netherlands
- Earliest CTIS Part Ii Submission Date
- 05-04-2024
- Latest Decision Or Authorization Date
- 09-10-2024
- Processing Time Days
- 187
- Number Of Sites
- 3
- Number Of Participants
- 44
Sites
- Site Name
- Stichting Amsterdam UMC
- Department Name
- Medical Oncology
- Contact Person Name
- Hanneke van Laarhoven
- Contact Person Email
- h.vanlaarhoven@amsterdamumc.nl
- Site Name
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Department Name
- Internist Oncology
- Contact Person Name
- Neeltje Steeghs
- Contact Person Email
- n.steeghs@nki.nl
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Inernist Oncology
- Contact Person Name
- Nadia Haj Mohammad
- Contact Person Email
- n.hajmohammad@umcutrecht.nl
Poland
- Earliest CTIS Part Ii Submission Date
- 05-04-2024
- Latest Decision Or Authorization Date
- 13-11-2024
- Processing Time Days
- 222
- Number Of Sites
- 8
- Number Of Participants
- 23
Sites
- Site Name
- Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie
- Department Name
- Oddział Onkologii Klinicznej z Pododdziałem Chemioterapii Jednodniowej
- Contact Person Name
- Mariusz Kwiatkowski
- Contact Person Email
- mariusz.kwiatkowski@swk.med.pl
- Site Name
- Specjalistyczny Szpital Onkologiczny Nu-Med Sp. z o.o.
- Department Name
- Oddzial Chemioterapii
- Contact Person Name
- Ewa Chmielowska
- Contact Person Email
- ewa.chmielowska@nu-med.pl
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
- Department Name
- Oddzial Kliniczny Onkologii
- Contact Person Name
- Piotr Wysocki
- Contact Person Email
- piotr.wysocki@uj.edu.pl
- Site Name
- Przychodnia Lekarska KOMED
- Contact Person Name
- Boguslawa Karaszewska
- Contact Person Email
- karasiowa@gmail.com
- Site Name
- Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
- Department Name
- Klinika Onkologii i Radioterapii
- Contact Person Name
- Lucjan Wyrwicz
- Contact Person Email
- lucjanwyrwicz@gmail.com
- Site Name
- Opolskie Centrum Onkologii Im. Prof. Tadeusza Koszarowskiego W Opolu Samodzielny Publiczny Zaklad Opieki Zdrowotnej
- Department Name
- Oddzial Onkologii Klinicznej
- Contact Person Name
- Barbara Radecka
- Contact Person Email
- brad@onkologia.opole.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Osrodek Badan Klinicznych Wczesnych Faz Uniwersyteckiego Centrum Klinicznego w Gdansku
- Contact Person Name
- Anna Kowalczyk
- Contact Person Email
- akow@gumed.edu.pl
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie (duplicate listing)
- Department Name
- Oddzial Kliniczny Onkologii
- Contact Person Name
- Piotr Wysocki
- Contact Person Email
- piotr.wysocki@uj.edu.pl
Sponsor
Primary sponsor
- Full Name
- AstraZeneca AB
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Sweden
Investigational products
- Investigational Product Name
- Rilvegostomig
- Active Substance
- RILVEGOSTOMIG
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Investigational Product Name
- volrustomig
- Active Substance
- VOLRUSTOMIG
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Investigational Product Name
- DS-8201a
- Active Substance
- TRASTUZUMAB DERUXTECAN
- Modality
- ADC
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Investigational Product Name
- IMFINZI 50 mg/mL concentrate for solution for infusion.
- Active Substance
- DURVALUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Authorisation Status
- Marketing authorisation: EU/1/18/1322/001
- Investigational Product Name
- PEMBROLIZUMAB
- Active Substance
- PEMBROLIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Investigational Product Name
- OXALIPLATIN
- Active Substance
- OXALIPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Investigational Product Name
- CAPECITABINE
- Active Substance
- CAPECITABINE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Investigational Product Name
- CISPLATIN
- Active Substance
- CISPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Investigational Product Name
- FLUOROURACIL
- Active Substance
- FLUOROURACIL
- Modality
- Small molecule
- Routes Of Administration
- SOLUTION FOR INJECTION OR INFUSION
- Route
- INTRAVENOUS
- Investigational Product Name
- TRASTUZUMAB
- Active Substance
- TRASTUZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Combination Treatment
- Yes
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