Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
835
Countries
12
Sites
56
Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient Metastatic Colorectal Cancer (dMMR)
All lines: 1) To compare PFS by BICR between nivolumab plus ipilimumab arm (arm B) vs nivolumab arm (arm A) 1L: 1) To compare PFS by BICR between nivolumab plus ipilimumab arm (arm B) vs chemotherapy arm (arm C)
Key facts
- Sponsor
- Bristol-Myers Squibb Services Unlimited Company
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 26 Aug 2019 → 24 Apr 2026
- Decision date (initial)
- 2024-05-02
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2023-503956-29-00
- EudraCT number
- 2018-000040-26
- WHO UTN
- U1111-1207-2702
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacogenomic, Pharmacokinetic, Efficacy, Pharmacodynamic, Therapy, Pharmacogenetic, Safety
All lines:
1) To compare PFS by BICR between nivolumab plus ipilimumab arm
(arm B) vs nivolumab arm (arm A)
1L:
1) To compare PFS by BICR between nivolumab plus ipilimumab arm
(arm B) vs chemotherapy arm (arm C)
Secondary objectives 5
- To compare: 1)ORR by BICR btw arm B vs arm A 2)OS btw arm B vs A
- To estimate: 3)PFS by investigator btw arm B vs A 4)PFS by BICR in locally determined dMMR/MSI-H mCRC btw arm B vs A
- 1L: To compare: 1)PFS by BICR btw arm B vs A 2)ORR by BICR btw arm B vs chemotherapy (arR by BICR btw arm B vs A 4)OS btw arm B vs A To estimate: 5)PFS by BICR btw arm A vs C 6)OS btw arm B vs C 7)ORR by BICR btw arm A vs C 8)OS btw arm A vs C 5)PFS by investigator by treatment arms (A, B, C) 9)PFS by BICR in locally determm C) 3)ORined dMMR/MSI-H mCRC btw arm B vs C 10)PFS by BICR in locally determined dMMR/MSI-H mCRC btw arm B vs A
- CDx (All lines and 1L):To estimate: 1)PFS by BICR in participants with confirmed dMMR/MSI-H mCRC by each central test in 1L setting btw arm B vs C 2)PFS by BICR in participants with confirmed dMMR/MSI-H mCRC by each central test across All lines btw arm B vs A
- Crossover cohort: To estimate: 1)PFS by BICR 2)ORR by BICR
Conditions and MedDRA coding
Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient Metastatic Colorectal Cancer (dMMR)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10052362 | Metastatic colorectal cancer | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Histologically confirmed recurrent or metastatic colorectal cancer (CRC) irrespective of prior treatment history with chemotherapy and/or targeted agents not amenable to surgery (Applicable only during Part 1 enrollment of the study)
- Histologically confirmed recurrent or metastatic CRC with no prior treatment history with chemotherapy and/or targeted agents for metastatic disease and not amenable to surgery (Applicable during Part 2 enrollment of the study)
- Known tumor MSI-H or dMMR status per local standard of practice
- Eastern cooperative oncology group (ECOG) performance status lower than or equal to 1
- Other protocol-defined inclusion/exclusion criteria apply
Exclusion criteria 4
- Participants with an active, known or suspected autoimmune disease
- History of interstitial lung disease or pneumonitis
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Other protocol-defined inclusion/exclusion criteria apply
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) (arm B vs A, all lines, centrally confirmed)
- PFS by BICR (arm B vs C, 1L, centrally confirmed)
Secondary endpoints 19
- Overall Response Rate (ORR) by BICR (arm B vs A, all lines, centrally confirmed)
- Overall Survival (OS) (arm B vs A, all lines, centrally confirmed)
- PFS by Investigator Assessment (arm B vs A, all lines, centrally confirmed)
- PFS by BICR among all randomized participants (arm B vs A, all lines, per local testing)
- PFS by BICR (arm B vs A, 1L, centrally confirmed)
- ORR by BICR (arm B vs C, 1L, centrally confirmed)
- ORR by BICR (arm B vs A, 1L, centrally confirmed)
- OS (arm B vs A, 1L, centrally confirmed)
- PFS by BICR (arm A vs C, 1L, centrally confirmed)
- OS (arm B vs C, 1L, centrally confirmed)
- ORR by BICR (arm A vs C, 1L, centrally confirmed)
- OS (arm A vs C, 1L, centrally confirmed)
- PFS by Investigator (arm A, B and C, 1L, centrally confirmed)
- PFS by BICR among all randomized participants who have not received prior treatment (arm B vs C, 1L, per local testing)
- PFS by BICR among all randomized participants who have not received prior treatment (arm B vs A, 1L, per local testing)
- PFS by BICR (arm B vs C, 1L, by each central test)
- PFS by BICR (arm B vs A, all lines, by each central test)
- PFS by BICR (crossover cohort, centrally confirmed)
- ORR by BICR (crossover cohort, centrally confirmed)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 4
YERVOY 5 mg/ml concentrate for solution for infusion
PRD363872 · Product
- Active substance
- Ipilimumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1 mg/kg milligram(s)/kilogram
- Max total dose
- 999 mg/kg milligram(s)/kilogram
- Max treatment duration
- 999 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FX04 — -
- Marketing authorisation
- EU/1/11/698/002
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Clinical Supplies will be labelled and packaged for the use of the study
YERVOY 5 mg/ml concentrate for solution for infusion
PRD363755 · Product
- Active substance
- Ipilimumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1 mg/kg milligram(s)/kilogram
- Max total dose
- 999 mg/kg milligram(s)/kilogram
- Max treatment duration
- 999 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FX04 — -
- Marketing authorisation
- EU/1/11/698/001
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Clinical Supplies will be labelled and packaged for the use of the study
OPDIVO 10 mg/mL concentrate for solution for infusion.
PRD2941376 · Product
- Active substance
- Nivolumab
- Substance synonyms
- BMS936558, ABP 206
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 480 mg milligram(s)
- Max total dose
- 999 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FF01 — -
- Marketing authorisation
- EU/1/15/1014/001
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
OPDIVO 10 mg/mL concentrate for solution for infusion.
PRD2941377 · Product
- Active substance
- Nivolumab
- Substance synonyms
- BMS936558, ABP 206
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 480 mg milligram(s)
- Max total dose
- 999 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FF01 — -
- Marketing authorisation
- EU/1/15/1014/002
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 4
SUB07721MIG · Substance
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 2400 mg/m2 milligram(s)/sq. meter
- Max total dose
- 999 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Label for clinical use
SUB20566 · Substance
- Active substance
- Disodium Folinate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 400 mg/m2 milligram(s)/sq. meter
- Max total dose
- 999 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Label for clinical use
Irinotecan Bendalis 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung
PRD2947838 · Product
- Active substance
- Irinotecan Hydrochloride Trihydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 180 mg/m2 milligram(s)/sq. meter
- Max total dose
- 999 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XX19 — IRINOTECAN
- Marketing authorisation
- 78592.00.00
- MA holder
- BENDALIS GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Clinical overlabeling for the purpose of this trial
Avastin 25 mg/ml concentrate for solution for infusion
PRD2153901 · Product
- Active substance
- Bevacizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 5 mg/kg milligram(s)/kilogram
- Max total dose
- 999 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FG01 — -
- Marketing authorisation
- EU/1/04/300/001
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Clinical overlabeling for the purpose of this trial
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Bristol-Myers Squibb Services Unlimited Company
- Sponsor organisation
- Bristol-Myers Squibb Services Unlimited Company
- Address
- Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2
- City
- Dublin 15
- Postcode
- D15 T867
- Country
- Ireland
Scientific contact point
- Organisation
- Bristol-Myers Squibb Services Unlimited Company
- Contact name
- GSM-CT
Public contact point
- Organisation
- Bristol-Myers Squibb Services Unlimited Company
- Contact name
- GSM-CT
Third parties 21
| Organisation | City, country | Duties |
|---|---|---|
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Code 10, Other |
| Pathai Inc. ORG-100031209
|
Boston, United States | Other |
| Accenture Services Pvt. Ltd. ORL-000000127
|
Bengaluru, India | Other |
| Omnitrace Corp. ORG-100045579
|
Palm Beach Gardens, United States | On site monitoring, Code 12, Other |
| Biocartis ORG-100052705
|
Mechelen, Belgium | Other |
| Mosaic Laboratories LLC ORG-100042385
|
Lake Forest, United States | Other |
| Agilent Technologies, Inc. ORG-100024881
|
Santa Clara, United States | Other |
| Iqvia Inc. ORG-100010622
|
Durham, United States | On site monitoring, Code 10, Code 11, Code 12, Code 2, Data management, Code 8, Code 9 |
| Labcorp | Center for Molecular Biology and Pathology ORL-000005147
|
Durham, United States | Other |
| GREENPHIRE INC ORL-000009081
|
King of Prussia, United States | Other |
| LabCorp ORL-000002905
|
Torrance, United States | Other |
| Icon Laboratories Inc. ORG-100037135
|
Farmingdale, United States | Other, Other, Laboratory analysis |
| Azenta Germany GmbH ORG-100022621
|
Griesheim, Germany | Other |
| Wuxi Apptec Co. Ltd. ORG-100012470
|
Shanghai, China | Other |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Other |
| Myriad RBM Inc. ORG-100045698
|
Austin, United States | Other |
| Labcorp Central Laboratory Services LP ORG-100044131
|
Indianapolis, United States | Other, Laboratory analysis |
| Pathai Inc. ORG-100031209
|
Boston, United States | Other |
| Azenta US Inc. ORG-100016263
|
Indianapolis, United States | Other |
| Agilent Technologies, Inc. ORG-100024881
|
Santa Clara, United States | Other |
| Iqvia Laboratories Limited ORG-100042527
|
Livingston, United Kingdom | Other |
Locations
12 EU/EEA countries · 56 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ended | 12 | 5 |
| Belgium | Ended | 36 | 3 |
| Czechia | Ended | 23 | 3 |
| Denmark | Ended | 23 | 2 |
| France | Ended | 160 | 11 |
| Germany | Ended | 47 | 8 |
| Greece | Ended | 18 | 2 |
| Italy | Ended | 81 | 4 |
| Netherlands | Ended | 26 | 3 |
| Norway | Ended | 13 | 3 |
| Romania | Ended | 41 | 5 |
| Spain | Ended | 91 | 7 |
| Rest of world
Japan, United States, Canada, Australia, Brazil, Argentina, Chile, China, Turkey, United Kingdom
|
— | 264 | — |
Investigational sites
Medical University Of Vienna
Internal Medicine I, Waehringer Guertel 18-20, Alsergrund, Vienna
Gemeinnutzige Salzburger Landes kliniken Betriebsgesellschaft mbH
Internal Medicine III, Muellner Hauptstrasse 48, 5020, Salzburg
Landesklinikum Wiener Neustadt
Oncology, Corvinusring 3-5, 2700, Wiener Neustadt
Krankenhaus Der Barmherzigen Schwestern
Visceral Oncology Center, Seilerstaette 4, 4020, Linz
Medical University Of Graz
Internal Medicine/Oncology, Auenbruggerplatz 15, 8036, Graz
Imelda
Medical Oncology, Imeldalaan 9, 2820, Bonheiden
UZ Leuven
Medical Oncology, Herestraat 49, 3000, Leuven
Institut Jules Bordet
Medical Oncology, Mijlenmeersstraat 90, 1070, Anderlecht
Fakultni Nemocnice Hradec Kralove
Klinika onkologie a radioterapie, Sokolska 581, 500 03, Novy Hradec Kralove
Masarykuv Onkologicky Ustav
Klinika komplexni onkologicke pece, Zluty Kopec 543/7, Stare Brno, Brno-Stred
University Hospital Olomouc
Onkologicka klinika, Zdravotniku 248/7, 779 00, Olomouc
Sygehus Lillebaelt Vejle Sygehus
Hematology, Kabbeltoft 25, 7100, Vejle
Herlev Hospital
Oncolgy, Borgmester Ib Juuls Vej 31, 2730, Herlev
Besancon University Hospital Center
Oncologie, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Oscar Lambret
Hôpital Oscar Lambret, 3 Rue Frederic Combemale, 59000, Lille
Institut Regional Du Cancer De Montpellier
Oncologie médicale, 208 Avenue Des Apothicaires, 34298, Montpellier Cedex 5
Centre Hospitalier Universitaire De Toulouse
Oncologie médicale, 1 Avenue Du Professeur Jean Poulhes, Tsa 50032, Toulouse Cedex 9
Centre Hospitalier Regional De Marseille
Hôpital La Timone, 264 Rue Saint Pierre, 13005, Marseille
Hopital Saint Antoine
Oncologie médicale, 184 Rue Du Faubourg Saint Antoine, 75571, Paris Cedex 12
Centre Hospitalier Universitaire De Poitiers
Hépato Gastroentérologie, 2 Rue De La Miletrie, 86000, Poitiers
Centre Hospitalier Et Universitaire De Limoges
CHU Dupuytren, 2 Avenue Martin Luther King, 87000, Limoges
Centre Leon Berard
Oncologie médicale, 28 Rue Laennec, 69008, Lyon
Centre Hospitalier Universitaire De Bordeaux
Hôpital du Haut-Lévêque, Avenue De Magellan, 33600, Pessac
Centre Hospitalier Universitaire De Nantes
CHU Hôtel Dieu, 1 Place Alexis Ricordeau, 44000, Nantes
Asklepios Klinik Altona
Onkologie, Paul-Ehrlich-Strasse 1, Othmarschen, Hamburg
Technische Universitat Dresden
Medizinische Klinik und Poliklinik I, Fetscherstrasse 74, Johannstadt-Nord, Dresden
Klinikum der Universitaet Muenchen AöR
Department of Medical Oncology and Hematology, Marchioninistrasse 15, Hadern, Munich
Philipps University Marburg
Klinik für Hämatologie, Onkologie und Immunologie, Baldingerstrasse, 35043, Marburg
Haematologisch Onkologische Praxis Eppendorf
Medizinische Klinik, Eppendorfer Landstrasse 42, Eppendorf, Hamburg
Medizinische Hochschule Hannover Service GmbH
Klinik für Gastroenterologie, Hepatologie, Endokrinologie, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Universitaetsklinikum Essen AöR
Department of Medical Oncology, Hufelandstrasse 55, Holsterhausen, Essen
Universitaetsklinikum Heidelberg AöR
Department of Medical Oncology, Im Neuenheimer Feld 460, Neuenheim, Heidelberg
Athens Medical Center S.A.
Oncology Department, Adersen 1, 115 25, Athens
Metropolitan General Hospital Healthcare Facilities Operation And Management Single Member S.A.
D' Cardiology Department, Leoforos Mesogeion 264, 155 62, Cholargos
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
U.O.C. Oncologia Medica, Largo Francesco Vito 1, 00168, Rome
ASST Grande Ospedale Metropolitano Niguarda
S.C. Oncologia Falck - Dipartimento di Ematologia e Oncologia, Piazza Dell'ospedale Maggiore 3, 20162, Milan
Istituto Oncologico Veneto
S.S. Neoplasie Gastroenteriche - S.C. Oncologia Medica, Via Gattamelata 64, 35128, Padova
Ospedale Garibaldi
U.O.C. Oncologia Medica, Piazza Santa Maria Di Gesu, 95123, Catania
Universitair Medisch Centrum Utrecht
Medical Oncology, Heidelberglaan 100, 3584 CX, Utrecht
Academisch Medisch Centrum
Medical Oncology, Meibergdreef 9, 1105 AZ, Amsterdam
Netherlands Cancer Institute
Medical Oncology, Plesmanlaan 121, 1066 CX, Amsterdam
Helse Bergen HF
Department of Oncology, Jonas Lies Vei 65, 5021, Bergen
Akershus University Hospital
Oncology Department, Sykehusveien 25, 1474, Loerenskog
Oslo University Hospital HF
Department of Oncology, Radiumhospitalet, Taarnbygget, Kirkeveien 166, Oslo
Institutul Regional De Oncologie Iasi
Medical Oncology, Strada G-Ral Berthelot 2-4, 700483, Iasi
Institutul Clinic Fundeni
Medical Oncology, Soseaua Fundeni 258, 022328, Bucharest
Spitalul Judetean De Urgenta Sfantul Ioan Cel Nou Suceava
Medical Oncology, Bulevardul 1 Decembrie 1918 21, 720237, Suceava
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca
Medical Oncology, Strada Republicii 34-36, 400015, Cluj-Napoca
Centrul De Oncologie SF Nectarie S.R.L.
Medical Oncology, Strada Caracal Nr 109, 200542, Craiova
Hospital Universitario 12 De Octubre
MEDICAL ONCOLOGY, Bloque D, Avenida De Cordoba S/n, Madrid
Complejo Universitario Juan Canalejo
ONCOLOGY, C As Xubias 84, 15006, A Coruna
Catalan Institute Of Oncology
MEDICAL ONCOLOGY, Carretera Canyet S/n, 08916, Badalona
University Hospital Virgen Del Rocio S.L.
ONCOLOGY, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Universitario Regional De Malaga
ONCOLOGY, Avenida De Carlos De Haya S/n, 29010, Malaga
Hospital General Universitario De Valencia
ONCOLOGY, Avenida Del Tres Cruces S/n, 46014, Valencia
Hospital Universitari Vall D Hebron
ONCOLOGY, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2019-10-04 | 2026-04-22 | 2019-11-26 | 2023-02-24 | |
| Belgium | 2019-11-06 | 2026-04-20 | 2019-11-06 | 2023-02-24 | |
| Czechia | 2019-11-19 | 2026-04-16 | 2019-12-10 | 2023-02-24 | |
| Denmark | 2019-09-23 | 2026-04-13 | 2019-09-26 | 2023-02-24 | |
| France | 2019-08-26 | 2026-04-22 | 2019-09-06 | 2023-02-24 | |
| Germany | 2019-10-29 | 2026-04-22 | 2019-11-11 | 2023-02-24 | |
| Greece | 2024-05-22 | 2026-04-21 | 2024-05-23 | 2024-05-24 | |
| Italy | 2019-09-25 | 2026-04-23 | 2019-10-10 | 2023-02-24 | |
| Netherlands | 2019-10-16 | 2026-04-21 | 2019-10-18 | 2023-02-24 | |
| Norway | 2019-11-14 | 2026-04-13 | 2019-11-18 | 2023-02-24 | |
| Romania | 2020-05-29 | 2026-04-22 | 2020-06-23 | 2023-02-24 | |
| Spain | 2019-09-30 | 2026-04-22 | 2019-10-01 | 2023-02-24 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 138 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-14-3-3-narratives-part1-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-14-3-3-narratives-part2-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-14-3-3-narratives-part3-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-14-3-3-narratives-part4-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-14-figures-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-14-tables-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-app-16-1-1-protamend09-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-app-16-1-2-sam-crf-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-app-16-1-9-statplan-v3-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-report-body-redacted | 1 |
| Clinical study report (for publication) | 2023-503956-29-00 ca2098hw-interim-csr-synopsis-redacted | 1 |
| Protocol (for publication) | D1_Protocol 2023-503956-29-00 GR Redacted | 10 |
| Protocol (for publication) | D1_Protocol 2023-503956-29-00_Clean | N/A |
| Protocol (for publication) | D1_Protocol 2023-503956-29-00_Redacted | 10 |
| Protocol (for publication) | D1_Protocol Administrative Letter_2023-503956-29-00_redacted | 7 |
| Recruitment arrangements (for publication) | K Recruitment arrangement_Blank Statement_Not to be redact | 1 |
| Recruitment arrangements (for publication) | K1 Recruitment Arrangement statement_No redaction | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed Consent Procedures Form_blank statement_BE_redacted | NA |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed Consent Procedures Form_blank statement_ES | NA |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed Consent Procedures Form_blank statement_FR | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed Consent Procedures Form_blank statement_IT | NA |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed Consent Procedures Form_blank statement_NL_redacted | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_AT | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_CZ | N/A |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_DE | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_GR | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_RO | 1 |
| Subject information and informed consent form (for publication) | L1 Cross over IC _Redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1 IC main_Redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1 ICF add 1 to cross over ICF_Redacted | 1 |
| Subject information and informed consent form (for publication) | L1 ICF add 1 to main ICF_Redacted | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF for Pregnant Partners GR Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Addendum for participants in Arms A_B_C GR | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Addendum for participants in Crossover Cohort GR | 2.1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF for Greenphire GR Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF for Optional Genetic Research GR Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF for Tretment beyond Progression GR | 2.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Main arm ABC_Redacted | 6 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Main Crossover_Redacted | 6 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Main for participants in Arm A_B_C GR Redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Main for participants in Crossover Cohort GR Redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Optional Tumor Biopsy_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Pregnant partner_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Treatm beyond prog_No redaction | 2 |
| Subject information and informed consent form (for publication) | L1_IT_SIS and ICF_Pregnant Partner_IT_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF _Optional Tumor Biopsy_ES_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF _Pregnant Partner_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum 1_CZ_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum 2_CZ_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum 3_CZ_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum 4_CZ_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum 5_CZ | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum 6_CZ | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum Arms A B and C_ES_Redacted | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum crossover 1_CZ_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum crossover 2_CZ_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum crossover 3_CZ_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum Crossover Cohort_ES_Redacted | 6 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum Treatment Beyond Progression_ES_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Additionnal 03 crossover_20220128_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Additionnal Treatment beyong progression_FR_20200921 | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Crossover Cohort_NL NLD_Redacted | 12.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Crossover ICF BE ENG_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Crossover ICF BE FRA_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Crossover ICF BE NLD_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Crossover_Addendum_IT | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Arms A B and C_ES_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Arms A B C_Addendum_IT | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Arms ABC_NL_NLD_Redacted | 12 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Crossover Cohort_ES_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main ICF BE ENG_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main ICF BE FRA_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main ICF BE NLD_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_FR_20220913_Redacted | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Biopsy at Progression_NL_NLD_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Biopsy on Treatment_NL_NLD_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Biopsy_FR_20200909_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Tumour Biopsy ICF_BE ENG_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Tumour Biopsy ICF_BE FRA_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Tumour Biopsy ICF_BE NLD_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant partner ICF_BE ENG_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant partner ICF_BE FRA_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant partner ICF_BE NLD_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Treatment Beyond Progression ICF_BE ENG_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Treatment Beyond Progression ICF_BE FRA_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Treatment Beyond Progression ICF_BE NLD_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Treatment Beyond Progression_NL_NLD_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Additional ICF_CZ_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Crossover Addendum_ger_AT | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Crossover Addendum_ger_DE | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Crossover ICF_CZ_Redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Crossover_ger_AT_redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Crossover_ger_DE_redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Crossover_IT_Redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ABC Addendum_ger_AT | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ABC Addendum_ger_DE | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ABC_ger_AT_redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ABC_ger_DE_redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main Arms A B C_IT_Redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_CZ_Redacted | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_OB_ger_AT_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_OB_ger_DE_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Optional ICF1_CZ_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Optional ICF2_CZ_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TBP_ger_AT | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TBP_ger_DE | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TBP_IT | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Treatment beyond progression ICF_CZ | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Withdrawal_IT_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_Sponsorship transition patient notification letter_ES | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_CN_CZ_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_information sheet for participants_FR | 1.0 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF_site contact details_ger_AT_clean | 07 |
| Subject information and informed consent form (for publication) | SIS and ICF addendum Arms ABC | 3.0A |
| Subject information and informed consent form (for publication) | SIS and ICF addendum Crossover | 3.0B |
| Subject information and informed consent form (for publication) | SIS and ICF Greenphire | 2 |
| Subject information and informed consent form (for publication) | SIS and ICF Main_Arms ABC_Redacted | 6.0A |
| Subject information and informed consent form (for publication) | SIS and ICF Main_Crossover_Redacted | 6.0B |
| Subject information and informed consent form (for publication) | SIS and ICF Optional Biopsy Addendum _Redacted | 02 |
| Subject information and informed consent form (for publication) | SIS and ICF pregnant partner_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | SIS and TBP ICF Addendum | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPc_Avastin | 67 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Fluorouracil Accord | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Irinotecan Hydrochloride-Accord | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Smpc_Sodiofolin medac | N/A |
| Synopsis of the protocol (for publication) | D1_IT_Protocol Synopsis_2023-503956-29 | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis BE EU CT 2023-503956-29-00_FRE | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis BE EU CT 2023-503956-29-00_GER | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis BE EU CT number 2023-503956-29-00_NLD | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis EU CT 2023-503956-29_NO | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis Greece EU CT No 2023-503956-29 | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis NL EU CT number 2023-503956-29-00_NLD | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-503956-29_AT_ger | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-503956-29_CZ | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-503956-29_FR | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_EU CT 2023-503956-29 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_RO_EUCT 2023-503956-29 | 1 |
| Synopsis of the protocol (for publication) | D1-Protocol synopsis-EU CT 2023-503956-29-00_v1_1Jul2024_ES | 1 |
Application history
20 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-29 | Czechia | Acceptable 2024-04-05
|
2024-04-05 |
| 2 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-05-29 | Acceptable | 2024-06-21 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-06-11 | Acceptable | 2024-07-26 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-06-11 | Acceptable | 2024-06-26 | |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-07-29 | Acceptable | 2024-07-29 | |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2024-08-02 | Czechia | Acceptable 2024-11-08
|
2024-11-08 |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2024-12-06 | Acceptable | 2025-01-21 | |
| 8 | SUBSTANTIAL MODIFICATION | SM-7 | 2024-12-13 | Acceptable | 2025-01-02 | |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-01-30 | Acceptable | 2025-01-30 | |
| 10 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-02-03 | Acceptable | 2025-02-03 | |
| 11 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2025-02-10 | Acceptable | 2025-02-10 | |
| 12 | NON SUBSTANTIAL MODIFICATION | NSM-6 | 2025-02-28 | Acceptable | 2025-02-28 | |
| 13 | NON SUBSTANTIAL MODIFICATION | NSM-7 | 2025-04-04 | Czechia | Acceptable | 2025-04-04 |
| 14 | SUBSTANTIAL MODIFICATION | SM-8 | 2025-06-10 | Czechia | Acceptable 2025-09-11
|
2025-09-11 |
| 15 | SUBSTANTIAL MODIFICATION | SM-9 | 2025-10-07 | Czechia | Acceptable 2025-12-03
|
2025-12-03 |
| 16 | SUBSTANTIAL MODIFICATION | SM-10 | 2025-12-22 | Czechia | Acceptable 2026-02-02
|
2026-02-02 |
| 17 | SUBSTANTIAL MODIFICATION | SM-11 | 2026-02-26 | Czechia | Acceptable 2026-04-28
|
2026-04-28 |
| 18 | NON SUBSTANTIAL MODIFICATION | NSM-8 | 2026-05-05 | Acceptable 2026-04-28
|
2026-05-05 | |
| 19 | NON SUBSTANTIAL MODIFICATION | NSM-9 | 2026-05-08 | Czechia | Acceptable 2026-04-28
|
2026-05-08 |
| 20 | NON SUBSTANTIAL MODIFICATION | NSM-10 | 2026-05-08 | Czechia | Acceptable 2026-04-28
|
2026-05-08 |