Clinical trial • Phase I/II • Oncology|Gastroenterology

PEMBROLIZUMAB for MSI-H/dMMR gastric cancer|MSI-H/dMMR gastroesophageal-junction cancer

Phase I/II trial of PEMBROLIZUMAB for MSI-H/dMMR gastric cancer|MSI-H/dMMR gastroesophageal-junction cancer.

Overview

Trial Therapeutic Area
Oncology|Gastroenterology
Trial Disease
MSI-H/dMMR gastric cancer|MSI-H/dMMR gastroesophageal-junction cancer
Trial Stage
Phase I/II
Drug Modality
Monoclonal antibody

Key dates

Initial CTIS Submission Date
15-01-2024
First CTIS Authorization Date
08-05-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial in Austria, Hungary, Denmark and others.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, Phase 1b includes a safety lead-in / dose-escalation to identify a recommended Phase 2 dose (RP2D) of S095029 in combination with pembrolizumab; specific escalation rules or stopping rules not provided in the available data.
Biomarker Stratified
True, biomarker: MSI-H/dMMR
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
26

Eligibility

Recruits 26 adults.

Inclusion criteria

  • {"criterion_text":"- Participants must have a histologically or cytologically confirmed diagnosis of a locally advanced and unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.\n- Participants’ tumor must have an MSI-H/dMMR status according to institutional guidelines and/or according to the College of American Pathologists, determined at any time prior to enrolment. This status may be documented in a report in the participant’s medical history or the MSI-H/dMMR status may be documented by testing archival tumor tissue or tissue from a newly collected tumor biopsy (if no appropriate archived specimen is available)."}

Exclusion criteria

  • {"criterion_text":"- Has received prior therapy with any checkpoint inhibitor (anti-PD-1, anti-programmed cell death ligand 1 (PDL1), anti-CTLA4).\n- Has received more than one previous line of treatment in the locally advanced and unresectable or metastatic setting. Previous treatment line may include trastuzumab and chemotherapy, or doublet/triplet chemotherapy regimens. Note: participants who have received only one cycle of chemotherapy prior to determination of their tumor’s MSI-H status, and who have not yet been treated with an anti-PD-1/L1 agent are not considered to have had one prior line of treatment. Previous treatment with chemotherapy in the neoadjuvant or adjuvant setting is permitted and is not counted as a previous line of therapy for the purpose of determining a patient’s eligibility.\n- Participants who have received prior systemic anti-cancer therapy including investigational agents within 4 weeks (shorter interval, at least 5 half-lives, for kinase inhibitors or other short half-life drugs), prior to first study treatment.\n- Prior radiotherapy if completed less than 2 weeks before first study treatment or have had a history of radiation pneumonitis. Participants who have not recovered from all radiation-related toxicities and require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.\n- Major surgery less than 4 weeks prior to the first study treatment or participants who have not recovered from the side effects of the surgery."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Phase 1b and Phase 2: Incidence of dose-limiting toxicities (DLTs).","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Phase 1b and Phase 2: Frequency and severity of adverse events (AEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0).","definition_or_measurement_approach":"AEs and laboratory abnormalities graded and reported according to NCI-CTCAE v5.0"}
  • {"endpoint_text":"- Phase 1b and Phase 2: Incidence of AEs leading to dose interruption, modification, delays and permanent treatment discontinuation.","definition_or_measurement_approach":"Incidence measured as number/proportion of participants with AEs causing dose interruption/modification/delay or permanent discontinuation (as reported by investigator)"}
  • {"endpoint_text":"- Phase 1b and Phase 2: Change from baseline to the end of the study in safety laboratory values and vital signs.","definition_or_measurement_approach":"Change from baseline to end of study in laboratory safety values and vital signs (as measured in protocol-specified safety labs and vitals)"}
  • {"endpoint_text":"- Phase 2: Objective response (OR) per investigator assessment using RECIST v1.1.","definition_or_measurement_approach":"Objective response assessed by investigator using RECIST v1.1"}

Secondary endpoints

  • {"endpoint_text":"- Phase 1b: Objective response (OR), duration of response (DoR), progression-free survival (PFS), and disease control (DC) according to RECIST v1.1 and iRECIST as assessed by investigator.","definition_or_measurement_approach":"Response and time-to-event endpoints assessed per RECIST v1.1 and iRECIST by investigator"}
  • {"endpoint_text":"- Phase 1b and Phase 2: Overall survival (OS) per investigator assessment.","definition_or_measurement_approach":"Overall survival measured from date of first study treatment to date of death (investigator assessment)"}
  • {"endpoint_text":"- Phase 1b and Phase 2: Serum concentrations of S095029","definition_or_measurement_approach":"Serum PK concentrations of S095029 measured at protocol-specified timepoints"}
  • {"endpoint_text":"- Phase 1b and Phase 2: Concentration of potential antibodies directed against S095029.","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADA) against S095029 at protocol-specified timepoints"}
  • {"endpoint_text":"- Phase 2: DoR, PFS, and DC according to RECIST v1.1 as assessed by investigator.","definition_or_measurement_approach":"Duration of response, progression-free survival and disease control assessed per RECIST v1.1 by investigator"}
  • {"endpoint_text":"- Phase 2: OR, DoR, PFS, and DC according to iRECIST criteria as per investigator assessment.","definition_or_measurement_approach":"Objective response, DoR, PFS and DC assessed per iRECIST by investigator"}

Recruitment

Planned Sample Size
26
Recruitment Window Months
62
Consent Approach
Written informed consent is obtained from participants. Subject information sheets and informed consent forms (ICFs) are provided; ICFs and related subject information materials are available in multiple languages (examples in the dossier: English, Spanish, French, Italian, German, Hungarian, Dutch, Polish). Optional and partner/pregnant-partner information and optional genetic/optional-analysis consent materials are included in site-specific ICF packages.

Geography

Total Number Of Sites
27
Total Number Of Participants
31

Austria

Earliest CTIS Part Ii Submission Date
25-04-2024
Latest Decision Or Authorization Date
07-07-2025
Processing Time Days
438
Number Of Sites
3
Number Of Participants
4

Sites

Site Name
SCRI CCCIT Ges.m.b.H.
Department Name
3.Medical Dept. with Hematology,Medical Oncology,Hemostaseology,Infectious Disease and Rheumatology
Principal Investigator Name
Florian Huemer
Principal Investigator Email
f.huemer@salk.at
Contact Person Name
Florian Huemer
Contact Person Email
f.huemer@salk.at
Site Name
Medical University Of Vienna
Department Name
Department of Medicine I, Division of Oncology
Principal Investigator Name
Aysegül Ilhan-Mutlu
Principal Investigator Email
aysegul.ilhan@meduniwien.ac.at
Contact Person Name
Aysegül Ilhan-Mutlu
Contact Person Email
aysegul.ilhan@meduniwien.ac.at
Site Name
Ordensklinikum Linz GmbH
Department Name
Internal Medicine I: Medical Oncology and Hematology
Principal Investigator Name
Holger Rumpold
Principal Investigator Email
Holger.Rumpold@ordensklinikum.at
Contact Person Name
Holger Rumpold

Hungary

Earliest CTIS Part Ii Submission Date
26-04-2024
Latest Decision Or Authorization Date
03-07-2025
Processing Time Days
433
Number Of Sites
4
Number Of Participants
3

Sites

Site Name
Semmelweis Egyetem
Department Name
Belgyógyászati és Onkológiai Klinika Onkológiai Részleg
Principal Investigator Name
Gyöngyvér Szentmártoni
Contact Person Name
Gyöngyvér Szentmártoni
Site Name
Clinexpert Kft.
Department Name
-
Principal Investigator Name
Itván Láng
Principal Investigator Email
prof.lang.istvan@clinexpert.hu
Contact Person Name
Itván Láng
Contact Person Email
prof.lang.istvan@clinexpert.hu
Site Name
Orszagos Onkologiai Intezet
Department Name
Mellkasi és hasüregi daganatok és klinikai farmakológiai osztály Kemoterápia B
Principal Investigator Name
Tamás Pintér
Principal Investigator Email
pinter.tamas@oncol.hu
Contact Person Name
Tamás Pintér
Contact Person Email
pinter.tamas@oncol.hu
Site Name
Bekes Varmegyei Koezponti Korhaz
Department Name
Onkológia
Principal Investigator Name
Lászó TORDAY
Principal Investigator Email
torday.laszlo@bmkk.eu
Contact Person Name
Lászó TORDAY
Contact Person Email
torday.laszlo@bmkk.eu

Denmark

Earliest CTIS Part Ii Submission Date
22-04-2024
Latest Decision Or Authorization Date
17-03-2026
Processing Time Days
694
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Rigshospitalet
Department Name
Department of Oncology
Principal Investigator Name
Martin Højgaard
Principal Investigator Email
martin.hoejgaard@regionh.dk
Contact Person Name
Martin Højgaard
Contact Person Email
martin.hoejgaard@regionh.dk
Site Name
Odense University Hospital
Department Name
Department of Oncology
Principal Investigator Name
Line Tarpgaard
Principal Investigator Email
line.tarpgaard@rsyd.dk
Contact Person Name
Line Tarpgaard
Contact Person Email
line.tarpgaard@rsyd.dk

Italy

Earliest CTIS Part Ii Submission Date
01-04-2024
Latest Decision Or Authorization Date
20-03-2026
Processing Time Days
718
Number Of Sites
5
Number Of Participants
5

Sites

Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Department Name
Investigational Cancer Therapeutics Clinical Unit, Head Section of Medical Oncology
Principal Investigator Name
Davide Melisi
Principal Investigator Email
davide.melisi@univr.it
Contact Person Name
Davide Melisi
Contact Person Email
davide.melisi@univr.it
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
UOC Oncoematologia
Principal Investigator Name
Fortunato Ciardiello
Principal Investigator Email
fortunato.ciardiello@unicampania.it
Contact Person Name
Fortunato Ciardiello
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
U.O. Oncologia Medica 2 Universitaria
Principal Investigator Name
Chiara Cremolini
Principal Investigator Email
chiaracremolini@gmail.com
Contact Person Name
Chiara Cremolini
Contact Person Email
chiaracremolini@gmail.com
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.S. Oncologia Medica Gastroenterologia
Principal Investigator Name
Filippo Pietrantonio
Principal Investigator Email
filippo.pietrantonio@istitutotumori.mi.it
Contact Person Name
Filippo Pietrantonio
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Clinical Trial Center
Principal Investigator Name
Gennaro Daniele
Principal Investigator Email
gennaro.daniele@policlinicogemelli.it
Contact Person Name
Gennaro Daniele

Spain

Earliest CTIS Part Ii Submission Date
18-04-2024
Latest Decision Or Authorization Date
23-03-2026
Processing Time Days
704
Number Of Sites
4
Number Of Participants
5

Sites

Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Medical Oncology
Principal Investigator Name
Aitana Calvo
Principal Investigator Email
pilaraitana.calvo@salud.madrid.org
Contact Person Name
Aitana Calvo
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology
Principal Investigator Name
Daniel Acosta
Principal Investigator Email
dacosta@vhio.net
Contact Person Name
Daniel Acosta
Contact Person Email
dacosta@vhio.net
Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Medical Oncology
Principal Investigator Name
Fernando Rivera
Principal Investigator Email
fernando.rivera@scsalud.es
Contact Person Name
Fernando Rivera
Contact Person Email
fernando.rivera@scsalud.es
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Medical Oncology
Principal Investigator Name
Tania Fleitas
Principal Investigator Email
tfleitas@incliva.es
Contact Person Name
Tania Fleitas
Contact Person Email
tfleitas@incliva.es

France

Earliest CTIS Part Ii Submission Date
23-04-2024
Latest Decision Or Authorization Date
25-03-2026
Processing Time Days
701
Number Of Sites
7
Number Of Participants
6

Sites

Site Name
Institut Gustave Roussy
Department Name
Département d’Innovation Thérapeutique et d’Essais Précoces – DITEP
Principal Investigator Name
Antoine HOLLEBECQUE
Principal Investigator Email
antoine.hollebecque@gustaveroussy.fr
Contact Person Name
Antoine HOLLEBECQUE
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Centre d’Investigation Clinique
Principal Investigator Name
Anthony TURPIN
Principal Investigator Email
Anthony.TURPIN@chu-lille.fr
Contact Person Name
Anthony TURPIN
Contact Person Email
Anthony.TURPIN@chu-lille.fr
Site Name
Institut Bergonie
Department Name
Département d'Oncologie Médicale
Principal Investigator Name
Simon PERNOT
Principal Investigator Email
s.pernot@bordeaux.unicancer.fr
Contact Person Name
Simon PERNOT
Contact Person Email
s.pernot@bordeaux.unicancer.fr
Site Name
Institut Curie
Department Name
Département d'Oncologie Médicale
Principal Investigator Name
Cindy NEUZILLET
Principal Investigator Email
cindy.neuzillet@curie.fr
Contact Person Name
Cindy NEUZILLET
Contact Person Email
cindy.neuzillet@curie.fr
Site Name
Institut De Cancerologie De Lorraine
Department Name
Département d'Oncologie Médicale
Principal Investigator Name
Aurélien LAMBERT
Principal Investigator Email
a.lambert@nancy.unicancer.fr
Contact Person Name
Aurélien LAMBERT
Contact Person Email
a.lambert@nancy.unicancer.fr
Site Name
Centr Georges Francois Leclerc
Department Name
Département d'Oncologie Médicale
Principal Investigator Name
François GHIRINGHELLI
Principal Investigator Email
fghiringhelli@cgfl.fr
Contact Person Name
François GHIRINGHELLI
Contact Person Email
fghiringhelli@cgfl.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Département d'Oncologie Médicale
Principal Investigator Name
Judith RAIMBOURG
Principal Investigator Email
judith.raimbourg@ico.unicancer.fr
Contact Person Name
Judith RAIMBOURG

Belgium

Earliest CTIS Part Ii Submission Date
23-04-2024
Latest Decision Or Authorization Date
19-03-2026
Processing Time Days
695
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Centre hospitalier universitaire de Liege
Department Name
Gastrology - Oncology
Principal Investigator Name
Catherine Loly
Principal Investigator Email
catherine.loly@chuliege.be
Contact Person Name
Catherine Loly
Contact Person Email
catherine.loly@chuliege.be
Site Name
UZ Leuven
Department Name
Gastroenterology, Digestive Oncology
Principal Investigator Name
Jeroen Dekervel
Principal Investigator Email
jeroen.dekervel@uzleuven.be
Contact Person Name
Jeroen Dekervel
Contact Person Email
jeroen.dekervel@uzleuven.be

Sponsor

Primary sponsor

Full Name
Institut De Recherches Internationales Servier IRIS
Organisation Type
Pharmaceutical company
Country Of Registered Address
France

Third parties

  • {"country":"United Kingdom","full_name":"Propath (UK) Limited","duties_or_roles":"Large Panel IF, HLA-E and PDL-1 expression by HIC in tumour biopsy","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Median Technologies","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Personalis Inc.","duties_or_roles":"PD and predictive biomarker assessment: (Biopsies and blood for genomics) for a comprehensive tissue immunogenomics profiling (MSI, TMB...)","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long term storage","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"Central Lab Logistics (Transferring the all of the sample for central lab analysis), ctDNA sample processing, temporary storage of the sample","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"Analytical laboratory for PK and ADA analysis in serum","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"Other Soluble factors testing in plasma","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"ctDNA dynamics monitoring: plasma for ctDNA","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
KEYTRUDA 25 mg/mL concentrate for solution for infusion
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
Authorised (Marketing authorisation: EU/1/15/1024/002)
Investigational Product Name
S095029/Sym025
Active Substance
SYM025
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Combination Treatment
Yes

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