Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
500
Countries
10
Sites
77
Advanced Breast Cancer
To demonstrate the superiority of saruparib (AZD5305) + camizestrant relative to physician's choice CDK4/6i + ET, by assessment of progression-free survival PFS in participants with Advanced Breast Cancer
Key facts
- Sponsor
- AstraZeneca AB
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 7 Apr 2025 → ongoing
- Decision date (initial)
- 2024-10-07
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- AstraZeneca AB
External identifiers
- EU CT number
- 2023-504180-16-00
- ClinicalTrials.gov
- NCT06380751
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Pharmacogenetic, Pharmacodynamic, Pharmacogenomic, Therapy, Pharmacokinetic, Safety
To demonstrate the superiority of saruparib (AZD5305) + camizestrant relative to physician's choice CDK4/6i + ET, by assessment of progression-free survival PFS in participants with Advanced Breast Cancer
Secondary objectives 1
- Key secondary: To demonstrate the superiority of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET by assessment of OS.
Conditions and MedDRA coding
Advanced Breast Cancer
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10072737 | Advanced breast cancer | 10029104 |
Regulatory references
- Scientific advice from competent authorities
- Food And Drug Administration, European Medicines Agency
- EMA paediatric investigation plan (PIP)
- EMEA-003447-PIP01-23
- Plan to share IPD
- Yes
- IPD plan description
- Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment : https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principies. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli .org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Adult females, pre/peri-menopausal and/or postmenopausal, and adult males
- Histologically or cytologically documented diagnosis of HRpositive, HER2-negative breast cancer
- Advanced breast cancer with either locally Advanced disease not amenable to curative treatment or metastatic disease
- ECOG performance status of O or 1 with no deterioration over the previous two weeks
- FFPE tissue from each participant (written confirmation of the availability can meet the study requirement for randomization) - Documented loss of function mutation in BRCA1, BRCA2,or PALB2, adhering to the following criteria a) Positive pre-existing local germline or tumour tissue result from an accredited laboratory appoved by theSponsor (CAP/CLIA, ISO15189 or equivalent); OR b) Positive result from prospective tumour tissue test performed at a central laboratory
- Adequate organ and marrow function
Exclusion criteria 22
- Participants with history of MDS/AML or with features suggestive of MDS/AML
- Participants with any known predisposition to bleeding
- Any history of persisting severe cytopenia
- Any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections
- Refractory nausea and vomiting, chronic GI disease, inability to swallow the formulated product, or previous significant bowel resection
- History of another primary malignancy
- Persistent toxicities (CTCAE Grade ~ 2) caused by previous anti-cancer therapy excluding alopecia
- Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease
- Evidence of active and uncontrolled hepatitis B and/or hepatitis C
- Evidence of active and uncontrolled HIV infection
- Active tuberculosis infection
- Cardiac criteria, including history of arrythmia and cardiovascular disease
- Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions.
- Major surgical procedure or significant traumatic injury within 4weeks of the first dose of study intervention oran anticipated need for major surgery during the study
- Palliative radiotherapy with a limited field of radiation within 2weeks or with wide field of radiation orto more than 30% of the bone marrow within 4 weeks before the first dose of study treatment
- Prior treatment with systemic anti-cancer therapy for locoregionally recurrent or metastatic disease is not permitted, apart from treatment with ET up to 28 days before randomisation
- Prior treatment within 28 days with blood product support or growth factor support
- Any systemic concurrent anti-cancer treatment
- Concomitant use of the following types of medications or herbal supplements within 21 days or at least 5 half-lives of randomisation: (a) Strong and moderate CYP3A4 inducers/inhibitors(b )Sensitive CYP2B6 substrates(c)Substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index, eg, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin.
- Concomitant use of drugs that are known to prolong QT and have a known risk of TdP
- Systemic use of atropine
- The following exclusion criteria apply to treatments administered for early breast cancer: (a)Disease progression s 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy (b)Disease progression </= 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer (c)Disease progression </= 1 year (365 days) from the last dose with aCDK4/6i in the adjuvant setting (d)Disease progression :s; 1 year (365 days) from the last dose of an oral SERD including camizestrant.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Progression-Free Survival defined as time from randomisation until progression per RECIST vl.1 as assessed by BICR, or death due to any cause.
Secondary endpoints 11
- Overall Survival defined as the time from randomisation until the date of death due to any cause.
- Progression Free Survival 2 defined as the time from randomisation to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.
- Time to chemotherapy defined as time from randomisation until the start date of the first subsequent chemotherapy treatment after discontinuation of randomised treatment (censoring participants who died prior to initiation of chemotherapy).
- Objective Response Rate defined as the proportion of participants who have a complete or partial response, as determined by BICR per RECIST vl.1.
- Duration of Response defined as the time from the date of first documented response until date of documented progression per RECIST vl.1 as assessed by BICR, or death due to any cause.
- Participant-reported tolerability defined as proportion of all dosed participants reporting different levels of severity of diarrhoea as measured by the diarrhoea single item (EORTCIL237 /IL239/IL240) and different levels of severity of abdominal pain as measured by the abdominal pain single item (EORTCIL237 /IL239/IL240).
- Time to deterioration in patient-reported global health status/QoL as measured by the global health status/QoL scale within the The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ).
- Change from baseline in patient-reported global health status/Qol as measured by the global health status/Qol scale within the The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)
- Plasma concentrations of saruparib (AZD5305)
- Plasma concentrations of camizestrant
- Samples will be used to develop companion diagnostics by analyzing their performance characteristics and calculate their consistency with clinical trial assays used for enrolment onto the study.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD10197822 · Product
- Active substance
- Saruparib
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- ASTRAZENECA AB
- Paediatric formulation
- No
- Orphan designation
- No
PRD9916833 · Product
- Active substance
- Camizestrant
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- ASTRAZENECA AB
- Paediatric formulation
- No
- Orphan designation
- No
Comparator 11
SUB05502MIG · Substance
- Active substance
- Anastrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- A ‘clinical tablet’ presentation is available. ARIMIDEX (anastrozole) clinical tablets, 1 mg are identical to the commercial formulation except for tablet intagliation, clinical trials packaging and labelling and shelf life. The modification to the appearance of the commercial product is considered not to affect the function, stability and efficacy of the comparator product. Reference is made to the approved marketed product for Quality information on the drug substance and drug product. Differences between the commercial drug product and the clinical drug product are presented in the sIMPD
SUB180246 · Substance
- Active substance
- Ribociclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use. Where AstraZeneca are providing sites with the authorised product it will be labelled and released by AstraZeneca prior to use in the clinical study.
SUB07492MIG · Substance
- Active substance
- Exemestane
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use. Where AstraZeneca are providing sites with the authorised product it will be labelled and released by AstraZeneca prior to use in the clinical study.
IBRANCE 125 mg film-coated tablets
PRD7907865 · Product
- Active substance
- Palbociclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EF01 — -
- Marketing authorisation
- EU/1/16/1147/014
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use.
IBRANCE 75 mg film-coated tablets
PRD7907995 · Product
- Active substance
- Palbociclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EF01 — -
- Marketing authorisation
- EU/1/16/1147/010
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use.
IBRANCE 100 mg film-coated tablets
PRD7907867 · Product
- Active substance
- Palbociclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EF01 — -
- Marketing authorisation
- EU/1/16/1147/012
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use.
SUB08444MIG · Substance
- Active substance
- Letrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use. Where AstraZeneca are providing sites with the authorised product it will be labelled and released by AstraZeneca prior to use in the clinical study.
Verzenios 50 mg film-coated tablets
PRD6701098 · Product
- Active substance
- Abemaciclib
- Substance synonyms
- LY2835219
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EF03 — -
- Marketing authorisation
- EU/1/18/1307/001
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use. Where AstraZeneca are providing sites with the authorised product it will be labelled and released by AstraZeneca prior to use in the clinical study
Verzenios 150 mg film-coated tablets
PRD6701108 · Product
- Active substance
- Abemaciclib
- Substance synonyms
- LY2835219
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EF03 — -
- Marketing authorisation
- EU/1/18/1307/007
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use. Where AstraZeneca are providing sites with the authorised product it will be labelled and released by AstraZeneca prior to use in the clinical study
Verzenios 100 mg film-coated tablets
PRD6701103 · Product
- Active substance
- Abemaciclib
- Substance synonyms
- LY2835219
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 88 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EF03 — -
- Marketing authorisation
- EU/1/18/1307/004
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use. Where AstraZeneca are providing sites with the authorised product it will be labelled and released by AstraZeneca prior to use in the clinical study
SUB13933MIG · Substance
- Active substance
- Fulvestrant
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAMUSCULAR
- Max daily dose
- 00 mg/ml milligram(s)/millilitre
- Max total dose
- 00 mg/ml milligram(s)/millilitre
- Max treatment duration
- 88 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The authorised drug product will be maintained in its original primary pack and will be secondary packed, re-labelled and QP certified by AstraZeneca prior to use. Where AstraZeneca are providing sites with the authorised product it will be labelled and released by AstraZeneca prior to use in the clinical study.
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
AstraZeneca AB
- Sponsor organisation
- AstraZeneca AB
- Address
- Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674
- City
- Sodertalje
- Postcode
- 151 85
- Country
- Sweden
Scientific contact point
- Organisation
- AstraZeneca AB
- Contact name
- AstraZeneca Clinical Study Information Center
Public contact point
- Organisation
- AstraZeneca AB
- Contact name
- AstraZeneca Clinical Study Information Center
Third parties 13
| Organisation | City, country | Duties |
|---|---|---|
| Fortrea Inc. ORG-100012602
|
Durham, United States | On site monitoring |
| Massive Bio Inc. ORG-100044618
|
New York, United States | Other |
| Guardant Health Inc. ORG-100042461
|
Redwood City, United States | Other |
| Signant Health Management Limited ORG-100040504
|
Reading, United Kingdom | Other |
| Yourgene Genomic Services Limited ORG-100047930
|
Manchester, United Kingdom | Other |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | Data management |
| Vivos Technology Limited ORG-100041363
|
London, United Kingdom | Code 10, Other |
| Labcorp Early Development Laboratories Inc. ORG-100012865
|
Madison, United States | Other |
| Almac Clinical Services Limited ORG-100017464
|
Craigavon, United Kingdom (Northern Ireland) | Other |
| Signant Health Global LLC ORG-100040604
|
Blue Bell, United States | Other |
| Covance Bioanalytical Services LLC ORG-100037229
|
Indianapolis, United States | Other |
| Myriad Genetics Inc. ORG-100046746
|
Salt Lake City, United States | Other |
| Perceptive Informatics Inc. ORG-100013171
|
Billerica, United States | Other |
Locations
10 EU/EEA countries · 77 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruiting | 9 | 4 |
| Bulgaria | Ongoing, recruiting | 8 | 3 |
| Czechia | Ongoing, recruiting | 12 | 6 |
| France | Ongoing, recruiting | 16 | 10 |
| Germany | Ongoing, recruiting | 22 | 15 |
| Hungary | Ongoing, recruiting | 8 | 6 |
| Italy | Ongoing, recruiting | 15 | 9 |
| Poland | Ongoing, recruiting | 13 | 8 |
| Portugal | Ongoing, recruiting | 11 | 6 |
| Spain | Ongoing, recruiting | 22 | 10 |
| Rest of world
India, Australia, Mexico, United States, Israel, China, Chile, Canada, Korea, Democratic People's Republic of, Brazil, United Kingdom, Malaysia, Japan, Thailand, Taiwan, Argentina, Peru, Turkey
|
— | 364 | — |
Investigational sites
Medical University Of Vienna
Universitätsklinik f. Innere Medizin I, Waehringer Guertel 18-20, Alsergrund, Vienna
Ordensklinikum Linz GmbH
Interne I: Medizinische Onkologie und Haematologie, Seilerstaette 4, 4010, Linz
Medical University Of Graz
Clinical Division for Oncology, Neue Stiftingtalstrasse 6, 8010, Graz
Medizinische Universitaet Innsbruck
University Clinic for Gynaecology and Obstetrics, Anichstrasse 35, 6020, Innsbruck
Complex Oncology Center Stara Zagora Ltd.
Department of Medical Oncology, Ulitsa Doktortodor Stoyanovich 15, 6003, Stara Zagora
Complex Oncological Center Plovdiv EOOD
Department of Medical Oncology and Oncological Diseases in Gastroenterology, Bulevard Aleksandir Stamboliyski 2a, 4004, Plovdiv
Uniteversity Muliprofile Hospital For Active Treatment Tsaritsa Yoanna-Isul EAD
Department of Medical Oncology, Oborishte Distr., Ul.Byalo More 8, Sofia
Fakultni Nemocnice Hradec Kralove
Clinic of radiology and oncology, Sokolska 581, 500 03, Novy Hradec Kralove
Multiscan s.r.o.
Oncology department, K Nemocnici 1106, 268 31, Horovice
Fakultni Nemocnice Bulovka
Oncology department, Budinova 67/2, Liben, Prague
Masarykuv Onkologicky Ustav
Department of clinical oncology, Zluty Kopec 543/7, Stare Brno, Brno-Stred
Vseobecna Fakultni Nemocnice V Praze
Oncology clinic, U Nemocnice 499/2, Nove Mesto, Prague
University Hospital Olomouc
Oncology clinic, Zdravotniku 248/7, 779 00, Olomouc
Institut Paoli Calmettes
Medical Oncology, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
Institut De Cancerologie De L Ouest
Medical Oncology, Boulevard Jacques Monod, 44805, Saint-Herblain Cedex
Centre Leon Berard
Medical Oncology, 28 Rue Laennec, 69008, Lyon
Centre Oscar Lambret
Medical Oncology, 3 Rue Frederic Combemale, 59000, Lille
CHU Besancon
medical oncology, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Institut Gustave Roussy
Medical Oncology and Hematology, 39 Rue Camille Desmoulins, 94805, Villejuif Cedex
Oncopole Claudius Regaud
Oncology, 1 Avenue Irene Joliot Curie, 31059, Toulouse Cedex 9
Institut De Cancerologie De L Ouest
Oncology, 15 Rue Andre Boquel, 49100, Angers
Centre Henri Becquerel
Medical Oncology, 1 Rue D Amiens, 76000, Rouen
Institut Curie
Oncology, 26 Rue D Ulm, 75005, Paris
Universitaetsklinikum Duesseldorf AöR
Frauenklinik, Moorenstrasse 5, Bilk, Duesseldorf
Universitaetsklinikum Muenster AöR
Universitätskrankenhaus Münster, Albert-Schweitzer-Campus 1, Sentrup, Muenster
RKH Klinken Ludwigsburg-Bietigheim gGmbH
Klinik für Frauenheilkunde und Geburtshilfe, Posilipostrasse 4, Mitte, Ludwigsburg
Universitaetsklinikum Schleswig-Holstein AöR
Klinik für Gynäkologie und Geburtshilfe, Arnold-Heller-Strasse 3, Brunswik, Kiel
Universitaetsklinikum Erlangen AöR
Frauenklinik, Universitaetsstrasse 21-23, Innenstadt, Erlangen
HELIOS Klinikum Berlin-Buch GmbH
Brustzentrum, Schwanebecker Chaussee 50, Buch, Berlin
Universitaetsklinikum Aachen AöR
Klinik für Gynäkologie und Geburtsmedizin, Pauwelsstrasse 30, 52074, Aachen
Universitaet Leipzig
Clinic and Policlinic for Gynaeocology, Liebigstrasse 20a, Zentrum-Suedost, Leipzig
Medizinische Hochschule Hannover
Klinik für Frauenheilkunde und Geburtshilfe, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Universitaetsmedizin Goettingen
Klinik für Gynäkologie und Geburtshilfe, Robert-Koch-Strasse 40, Weende, Goettingen
Staedtisches Klinikum Dessau
Klinik für Frauenheilkunde und Geburtshilfe, Auenweg 38, Alten, Dessau-Rosslau
Klinikum rechts der Isar der TU Muenchen AöR
Klinikum rechts der Isar der TU München, Ismaninger Strasse 22, Au-Haidhausen, Munich
Universitaetsklinikum Heidelberg AöR
Nationales Zentrum für Tumorerkrankungen (NCT), Im Neuenheimer Feld 460, Neuenheim, Heidelberg
Haematologie-Onkologie im Zentrum MVZ GmbH
Hämatologie-Onkologie Im Zentrum MVZ GmbH, Halderstrasse 29, Innenstadt, Augsburg
Mammazentrum Hamburg MVZ GbR
NA, Moorkamp 2-6, Eimsbuettel, Hamburg
University Of Debrecen
Oncology, Nagyerdei Korut 98, 4032, Debrecen
Budapesti Uzsoki Utcai Korhaz
Oncology, Uzsoki Utca 29-41, 1145, Budapest XIV
Semmelweis Egyetem
Belgyógyászati és Onkológiai Klinika, Baross Utca 23, 1082, Budapest
Orszagos Onkologiai Intezet
Oncology, Rath Gyorgy Utca 7-9, Kerulet, Budapest XII
Zala Varmegyei Szent Rafael Korhaz
Onkológiai Osztály, Zrinyi Miklos Utca 1, 8900, Zalaegerszeg
Borsod-Abauj-Zemplen Varmegyei Koezponti Korhaz Es Egyetemi Oktatokorhaz
Oncology, Szentpeteri Kapu 72-76, 3526, Miskolc
Humanitas Mirasole S.p.A.
Breast Oncology Unit, Via Alessandro Manzoni 56, 20089, Rozzano
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Precision Medicine in Senology, Largo Francesco Vito 1, 00168, Rome
Istituto Europeo Di Oncologia S.r.l.
Medical Senology, Via Giuseppe Ripamonti 435, 20141, Milan
Istituto Oncologico Veneto
Oncology 2, Via Gattamelata 64, 35128, Padova
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Oncology Disivion, Via Mariano Semmola 52, 80131, Naples
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
Onco Ematology at SC Ongologia, Piazza Oms 1, 24127, Bergamo
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Medical Oncology, Via Pietro Albertoni 15, 40138, Bologna
Azienda USL IRCCS Di Reggio Emilia
Medical Ongolory at Ongolofica Medica Provinciale, Viale Risorgimento 80, 42123, Reggio Emilia
Ospedale San Raffaele S.r.l.
Medical Oncology, Via Olgettina 60, 20132, Milan
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Klinika Nowotworów Piersi i Chirurgii Rekonstrukcyjnej, Ul. Wilhelma Konrada Roentgena 5, 02-781, Warsaw
Centrum Onkologii Ziemi Lubelskiej Im. Sw. Jana Z Dukli
I Oddził Onkologii Klinicznej z Chemioterapia Dzienna, Ul. Dra Kazimierza Jaczewskiego 7, 20-090, Lublin
Kliniki Neuroradiochirurgii Sp. z o.o.
Kliniczny Oddzial Chemioterapii, Ul. Uniwersytecka 6a, 26-601, Radom
Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie
Oddzial Dzienny Chemioterapii, Ul. Tytusa Chalubinskiego 7, 75-581, Koszalin
Uniwersytecki Szpital Kliniczny W Poznaniu
Oddzial Chemioterapii, Ul. Augustyna Szamarzewskiego 84, 60-569, Poznan
Centrum Medyczne Hcp Sp. z o.o.
Ośrodek Badań Klinicznych, Ul. 28 Czerwca 1956 R. 194, 61-485, Poznan
Wojewodzki Szpital Specjalistyczny W Bialej Podlaskiej
Oddział Onkologii Klinicznej, Ul. Terebelska 57/65, 21-500, Biala Podlaska
Instytut Centrum Zdrowia Matki Polki
Klinika Onkologii, Ul. Rzgowska 281/289, 93-338, Lodz
Instituto Portugues De Oncologia De Lisboa Francisco Gentil E.P.E.
Medical Oncology, Rua Professor Lima Basto, 1099-023, Lisbon
Unidade Local De Saude De Matosinhos E.P.E.
Medical Oncology, Rua Doutor Eduardo Torres, 4464-513, Senhora Da Hora
Unidade Local De Saude De Tras-Os-Montes E Alto Douro E.P.E.
Medical Oncology, Ulstmad, Avenida Da Noruega, Vila Real
Hospital Cuf Descobertas S.A.
Medical Oncology, Rua Mario Botas 1, 1998-018, Lisbon
Instituto Portugues De Oncologia De Coimbra Francisco Gentil E.P.E.
Medical Oncology, Avenida Doutor Bissaya Barreto 98, 3000-075, Coimbra
Hospital Lusiadas Porto
Medical Oncology, Avenida Da Boavista 171, 4050-115, Porto
Hospital Universitari Vall D Hebron
Oncology, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital San Pedro De Alcantara
Oncology, Avenida De Pablo Naranjo Porras S/n, 10002, Caceres
Institut Catala D'oncologia
Oncology, Avinguda De La Gran Via De L'hospitalet 199-203, 08908, L'hospitalet De Llobregat
Hospital Universitario Clinico San Cecilio
Oncology, Avenida Del Conocimiento S/n, Poligono Industrial De Ciencias De La Salud, Granada
Hospital Universitario Virgen De La Victoria
Oncology, Calle Del Arroyo Teatinos Sn, 29010, Malaga
Hospital Universitario De Navarra
Oncology, Irunlarrea Kalea 3, 31008, Pamplona
Hospital Clinico Universitario De Valencia
Oncology, Avenida Blasco Ibanez 17, 46010, Valencia
Hospital Clinico San Carlos
Oncology, Calle Del Profesor Martin Lagos Sn, 28040, Madrid
University Hospital Virgen Del Rocio S.L.
Oncology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Universitario 12 De Octubre
Oncology, Bloque D, Avenida De Cordoba Sn, Madrid
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 | 2025-04-23 | 2025-06-16 | |||
| Bulgaria | 2025-05-19 | 2025-08-14 | |||
| Czechia | 2025-10-22 | 2025-10-31 | |||
| France | 2025-06-12 | 2025-06-23 | |||
| Germany | 2025-04-07 | 2025-04-15 | |||
| Hungary | 2025-06-30 | 2025-08-04 | |||
| Italy | 2025-04-16 | 2025-04-24 | |||
| Poland | 2025-05-05 | 2025-06-02 | |||
| Portugal | 2025-07-08 | 2025-07-11 | |||
| Spain | 2025-04-15 | 2025-04-16 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Corrective measures 1 · Art. 77 CTR
Corrective measure CM-FR-0001
- Member state
- France
- Publication date
- 2025-03-20
- Type
- 3
- Reason
- 7
- Immediate action required
- Yes
- Justification
- The sponsor is requested to submit a specific SM part II only in france in order to update its CTA in line with the doucmentation approved during the appeal procedure within 10days afeter the submission of this corrective measure.
17/01/2025
As mentionned by sponsor, the SM could not be submitted within 10 days, due to the ongoing instruction of a SM part I and II.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 140 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023_504180_16_00_redacted | 4.1 |
| Protocol (for publication) | D4_ Patient facing document_questionnaire PGI TT_AT | 1 |
| Protocol (for publication) | D4_ Patient facing document_questionnaire PGI TT_DE | 1 |
| Protocol (for publication) | D4_ Patient facing document_questionnaire PGI TT_FR | 1 |
| Protocol (for publication) | D4_ Patient facing document_questionnaire PGI TT_HU | NA |
| Protocol (for publication) | D4_ Patient facing document_questionnaire PGI TT_PL | 1 |
| Protocol (for publication) | D4_ Patient facing document_questionnaire_PGI TT | 1 |
| Protocol (for publication) | D4_Patient facing document_questionnaire_PGI TT_BG | 1 |
| Protocol (for publication) | D4_Patient facing document_questionnaire_PGI TT_CZ | 1 |
| Protocol (for publication) | D4_Patient facing document_questionnaire_PGI TT_IT | 1 |
| Protocol (for publication) | D4_Patient facing document_questionnaire_PGI TT_PT | 1 |
| Recruitment arrangements (for publication) | K1_Investigators memo | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements Austria | 1.0 |
| Recruitment arrangements (for publication) | K2_ Patient facing documents_biomarker testing guide _FR | 1 |
| Recruitment arrangements (for publication) | K2_ Patient facing documents_pamphlet _FR | 1 |
| Recruitment arrangements (for publication) | K2_ Patient facing documents_patient guide_FR | 1 |
| Recruitment arrangements (for publication) | K2_ Patient facing documents_poster _FR | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment arrangements_Poster_BG | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material Biomaker Testing Guide_redacted | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material Biomarker Guide | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material Biomarker Guide Austria | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material Pamphlet | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material Pamphlet Austria | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material Pamphlet_redacted | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material Patient study Guide Austria | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material Patient Study Guide_redacted | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material Poster | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material poster | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material Poster Austria | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material Study Guide | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material_Biomarker testing guide | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Pamphlet | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material_Pamphlet | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material_Patient guide | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Poster | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Screening Guide | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Study Guide | 1.0 |
| Recruitment arrangements (for publication) | K2_Recuitment material_Poster | 1.0 |
| Recruitment arrangements (for publication) | Redacted Statement Document | NA |
| Recruitment arrangements (for publication) | Redacted Statement Document | NA |
| Recruitment arrangements (for publication) | Redacted Statement Document | NA |
| Subject information and informed consent form (for publication) | D1_Protocol Synopsis LL_HU_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF optional genetic research_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_Biomarker ICF_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_Pregnant Partner ICF | 2.0 |
| Subject information and informed consent form (for publication) | L1_Pregnant Partner ICF_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult Participants_redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Annex I to Main_Redacted | v5.0 EU v2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Annex II to Main_Redacted | v5.0 EU v2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker Future Research_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker Future Research_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker_BG_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker_EN_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biomarker_Redacted | v3.0 ES |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Future Optional Genetic Biomarker_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Future Optional Genetic_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Future Research_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Future Research_Redacted | v5.0 EU v2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Genetic Biomarker_Redacted | 3.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Genetic_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Genetic_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Genetic_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Genomic Initiative_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Future Research Germany_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Future Research_Redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_BG_Redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_EN_Redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | v5.0 EU v3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Genetic_BG_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Genetic_EN_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Genetic_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Genetic_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Participant_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_BG_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_EN_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Prescreening_redacted | 3.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Adult_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Biomarker Future Research_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Biomarker testing_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Biomarker_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Future Research_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Optional Genetics_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Privacy notice_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and Main ICF_Redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_Site Contact Details for ICF_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Brochure_PreS_BG | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP Letter_BG | 2.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP Letter_EN | 2.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Guide_PSG_BG | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Pamphlet_BG | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Patient card_BG | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Patient card_EN | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Study Participation Card | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Study Participation Card | 2.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Thank you card | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_TY | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information materials_Patient ID card | 2.0 |
| Subject information and informed consent form (for publication) | Redacted Statement Document | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Redacted Statement | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Redacted Statement | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Redacted Statement | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Redacted Statement | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Redacted Statement | 1 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_BGR_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_CZE_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_ES_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_FR_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_HU_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_IT_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_PL_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis_2023-504180-16-00_PT_Redacted | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol 2023_504180_16_00_lay_language_synopsis_redacted | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2023-504180-16-00_BGR_Redacted | 4.1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-504180-16-00_CZE_Redacted | 4.1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2023-504180-16-00_HU_Redacted | NA |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2023-504180-16-00_IT_Redacted | 4.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2023-504180-16-00_PL_Redacted | 4.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2023-504180-16-00_PT_Redacted | 4.1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_AT_2023-504180-16-00_Redacted | 4.0 |
Application history
12 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-07 | Germany | Acceptable with conditions 2024-09-30
|
2024-09-30 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2024-10-31 | Acceptable with conditions 2024-09-30
|
2024-10-31 | |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2024-11-21 | Germany | Acceptable with conditions 2024-09-30
|
2024-11-21 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-12-20 | Germany | Acceptable 2025-03-07
|
2025-03-10 |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-03-18 | Acceptable | 2025-04-22 | |
| 6 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-04-25 | Germany | Acceptable 2025-07-22
|
2025-07-23 |
| 7 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-08-13 | Acceptable | 2025-08-22 | |
| 8 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-08-18 | Acceptable | 2025-08-29 | |
| 9 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-09-23 | Germany | Acceptable 2025-12-16
|
2025-12-17 |
| 10 | SUBSTANTIAL MODIFICATION | SM-8 | 2026-01-13 | Germany | Acceptable 2026-02-27
|
2026-02-27 |
| 11 | SUBSTANTIAL MODIFICATION | SM-9 | 2026-03-27 | Acceptable | 2026-04-29 | |
| 12 | SUBSTANTIAL MODIFICATION | SM-10 | 2026-03-27 | Acceptable | 2026-04-21 |