Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
549
Countries
9
Sites
24
Incurable/Non-metastatic Hepatocellular Carcinoma
1.To compare pembrolizumab plus lenvatinib in combination with transarterial chemoembolization (TACE) versus placebo plus TACE with regard to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by blinded, independent central review (BICR). 2.To compare pem…
Key facts
- Sponsor
- Merck Sharp & Dohme LLC
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 10 Jul 2020 → 23 Mar 2026
- Decision date (initial)
- 2023-07-28
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- EISAI · Merck Sharp & Dohme LLC
External identifiers
- EU CT number
- 2022-502116-36-00
- EudraCT number
- 2019-002345-37
- WHO UTN
- U1111-1283-3439
- ClinicalTrials.gov
- NCT04246177
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Pharmacodynamic, Safety, Others, Pharmacokinetic
1.To compare pembrolizumab plus lenvatinib in combination with transarterial chemoembolization (TACE) versus placebo plus TACE with regard to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by blinded, independent central review (BICR).
2.To compare pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE with regard to overall survival (OS).
Secondary objectives 3
- To evaluate pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE with regard to PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and time to progression (TTP) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) assessed by BICR.
- To evaluate the safety and tolerability of pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE.
- To evaluate pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE with regard to efficacy outcomes per RECIST 1.1 assessed by BICR.
Conditions and MedDRA coding
Incurable/Non-metastatic Hepatocellular Carcinoma
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10073071 | Hepatocellular carcinoma | 100000004864 |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- Yes
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Has a diagnosis of hepatocellular carcinoma (HCC) confirmed by radiology, histology, or cytology
- Has HCC localized to the liver and not amenable to curative treatment
- Participants with Hepatitis C virus (HCV) are eligible if treatment was completed at least 1 month prior to starting study intervention
- Participants with Hepatitis B virus (HBV) are eligible
- Has adequately controlled blood pressure with or without antihypertensive medications
- Has adequate organ function
Exclusion criteria 6
- Is currently a candidate for liver transplantation
- Has had gastric bleeding within the last 6 months
- Has ascites that is not controlled with medication
- Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as congestive heart failure
- Has a serious nonhealing wound, ulcer, or bone fracture
- Has received locoregional therapy to existing liver lesions
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
- Overall Survival (OS)
Secondary endpoints 13
- PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
- Objective Response Rate (ORR) per mRECIST
- Disease Control Rate (DCR) per mRECIST
- Duration of Response (DOR) per mRECIST
- Time to Progression (TTP) per mRECIST
- Percentage of Participants Who Experience At Least One Adverse Event (AE)
- Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE)
- Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI)
- Percentage of Participants Who Discontinue Study Drug Due to an AE
- ORR per RECIST 1.1
- DCR per RECIST 1.1
- DOR per RECIST 1.1
- TTP per RECIST 1.1
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD9414230 · Product
- Active substance
- Lenvatinib
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 2920 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- MERCK & CO. INC.
- Paediatric formulation
- No
- Orphan designation
- No
KEYTRUDA 25 mg/mL concentrate for solution for infusion
PRD4323105 · Product
- Active substance
- Pembrolizumab
- Substance synonyms
- Lambrolizumab, MK-3475, SCH-900475, ABP 234
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 6800 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FF02 — -
- Marketing authorisation
- EU/1/15/1024/002
- MA holder
- MERCK SHARP & DOHME BV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 2
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Placebo for Keytruda, normal commercial saline
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 2
-
SCP242743 · ATC
- Route of administration
- INTRAARTERIAL USE
- Max daily dose
- 120 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 18 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01DB — ANTHRACYCLINES AND RELATED SUBSTANCES
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
SCP140972 · ATC
- Route of administration
- INTRAARTERIAL USE
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 18 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA — PLATINUM COMPOUNDS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Merck Sharp & Dohme LLC
- Sponsor organisation
- Merck Sharp & Dohme LLC
- Address
- 126 East Lincoln Avenue
- City
- Rahway
- Postcode
- 07065-4607
- Country
- United States
Scientific contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Leonid Dubrovsky
Public contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Leonid Dubrovsky
Third parties 10
| Organisation | City, country | Duties |
|---|---|---|
| Q2 Solutions ORL-000000243
|
West Lothian, United Kingdom | Laboratory analysis |
| PPD Laboratories ORL-000001474
|
Richmond, VA, United States | Laboratory analysis |
| Parexel International Corp. ORG-100007310
|
Auburndale, United States | Other |
| Signant ORL-000001475
|
Reading, United Kingdom | E-data capture |
| Almac Clinical Technologies LLC ORG-100043036
|
Souderton, United States | Interactive response technologies (IRT) |
| Q2 Solutions, 2 Squared Solutions LLC ORL-000001473
|
Valencia, CA, United States | Laboratory analysis |
| Perceptive Eclinical Limited ORG-100041144
|
Nottingham, United Kingdom | Other |
| Labcorp Drug Development Inc. ORG-100012602
|
Princeton, United States | Other |
| ICON Medical Imaging ORL-000001154
|
Blue Bell, United States | Other |
| Q2 Solutions Central Laboratories ORL-000001472
|
Middlesex, United Kingdom | Laboratory analysis |
Locations
9 EU/EEA countries · 24 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ended | 13 | 1 |
| France | Ended | 30 | 6 |
| Germany | Ended | 44 | 2 |
| Hungary | Ended | 12 | 1 |
| Ireland | Ended | 5 | 1 |
| Italy | Ended | 36 | 4 |
| Norway | Ended | 4 | 1 |
| Portugal | Ended | 26 | 2 |
| Spain | Ended | 30 | 6 |
| Rest of world
Ukraine, Hong Kong, Taiwan, China, Brazil, United States, New Zealand, Chile, United Kingdom, Korea, Republic of, Japan, Colombia, Australia, Israel, Puerto Rico, Thailand, Turkey
|
— | 349 | — |
Investigational sites
Region Midtjylland
Department of Oncology, Reseacrh unit, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
CHRU De Nancy
Service d’hépato-gastroentérologie, Rue Du Morvan, 54500, Vandoeuvre Les Nancy
Assistance Publique Hopitaux De Paris
Service Hépatologie, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex
Hospital La Croix Rousse Hcl
Service d’hépatologie et Gastroentérologie du Professeur Zoulim, 103 Grande Rue De La Croix Rousse, 69317, Lyon Cedex 04
Centre Hospitalier Universitaire De Bordeaux
Groupe SUD – Hôpital Haut-Lévêque, Avenue De Magellan, 33600, Pessac
Hopital Paul Brousse
Service d’hépatologie et transplantation hépatique, 12 Avenue Paul Vaillant Couturier, 94804, Villejuif Cedex
Assistance Publique Hopitaux De Marseille
NA, 264 Rue Saint Pierre, 13005, Marseille
Universitaetsklinikum Bonn AöR
Medizinische Klinik und Poliklinik I Onkologische Gastroenterologie, Venusberg-Campus 1, Venusberg, Bonn
University Hospital Halle (Saale)
Universitätsklinik und Poliklinik für Innere Medizin I, Ernst-Grube-Strasse 40, Kroellwitz, Halle Saale
Zala Varmegyei Szent Rafael Korhaz
Onkológiai Osztály, Zrinyi Miklos Utca 1, 8900, Zalaegerszeg
Azienda Unita Sanitaria Locale Della Romagna
Dipartimento Oncoematologico, Viale Vincenzo Randi 5, 48121, Ravenna
Azienda Unita Sanitaria Locale Della Romagna
U.O. Oncologia, Viale Stradone 9, 48018, Faenza
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
UOC Epatologia, Via Antonio Cardarelli 9, 80131, Naples
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
CENTRO MALATTIE APPARATO DIGERENTE– DIGESTIVE DISEASE CENTER, Largo Francesco Vito 1, 00168, Rome
Oslo University Hospital HF
Avdeling for kreftbehandling, Kreftklinikken, Montebello, Ullernchausséen 70, Oslo
Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E.
Departamento de Oncologia, Rua Dr. Antonio Bernardino De Almeida, 4200-072, Porto
Unidade Local De Saude De Sao Jose E.P.E.
Departamento de Oncologia, Rua Jose Antonio Serrano, 1150-199, Lisbon
Hospital General Universitario Gregorio Maranon
Servicio de Digestivo, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Clinico San Carlos
Servicio de Oncología Médica, Calle Del Profesor Martin Lagos S/n, 28040, Madrid
Hospital Universitario Puerta De Hierro De Majadahonda
Servicio de Gastroenterología, Calle De Manuel De Falla 1, 28222, Majadahonda
Hospital Universitario Ramon Y Cajal
Servicio de Gastroenterología, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
University Hospital Virgen Del Rocio S.L.
UGS - Aparato Digestivo, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital General Universitario De Valencia
Servicio de Hepatologia, Avenida Del Tres Cruces 2, 46014, Valencia
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 |
|---|---|---|---|---|---|
| Denmark | 2021-04-15 | 2025-02-27 | 2021-10-08 | 2022-12-30 | |
| France | 2020-07-10 | 2025-11-19 | 2020-07-16 | 2022-12-08 | |
| Germany | 2021-01-11 | 2021-07-19 | 2022-12-30 | ||
| Hungary | 2020-12-15 | 2025-01-09 | 2021-08-26 | 2022-12-30 | |
| Ireland | 2022-05-09 | 2025-11-14 | 2022-10-13 | 2022-11-16 | |
| Italy | 2020-10-28 | 2025-11-05 | 2021-07-15 | 2022-12-30 | |
| Norway | 2022-05-20 | 2025-11-18 | 2022-11-14 | 2022-12-30 | |
| Portugal | 2020-10-29 | 2025-11-06 | 2021-05-24 | 2022-12-27 | |
| Spain | 2020-07-23 | 2025-11-13 | 2020-10-13 | 2022-12-02 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 75 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2022-502116-36-00_for pub | 28NOV2022 |
| Protocol (for publication) | D4_Subject questionnaire_ePRO_DEU_DE_for pub | 1 |
| Protocol (for publication) | D4_Subject questionnaire_ePRO_ESP_ES_for pub | 22NOV2019 |
| Protocol (for publication) | D4_Subject questionnaire_ePRO_for pub | 23OCT2019 |
| Protocol (for publication) | D4_Subject questionnaire_ePRO_FRA_FR_for pub | 1 |
| Protocol (for publication) | D4_Subject questionnaire_ePRO_HUN_HU_for pub | 26NOV2019R |
| Protocol (for publication) | D4_Subject questionnaire_paper_EQ-5D-5L_FRA_FR_for pub | 1.0 |
| Protocol (for publication) | D4_Subject questionnaire_paper_QLQ-C30_FRA_FR_for pub | 2.0 |
| Protocol (for publication) | D4_Subject questionnaire_paper_QLQ-HCC18_FRA_FR_for pub | 1.0 |
| Recruitment arrangements (for publication) | CTIS Placeholder document | 03Nov2022 |
| Recruitment arrangements (for publication) | K1_Danish Attachment To Protocol_DNK_for pub | 06Feb2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_DEU_EN_for pub | 06DEC2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_FRA_EN_for pub | 29NOV2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_HUN_EN_for pub | 14NOV2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_IRL_EN_for pub | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_ITA_EN_for pub | 12DEC2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and ICF Procedure_NOR_EN_for pub | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_ESP_ES_for pub | 18DEC2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Brochure_ESP_ES_for pub | 00 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Brochure_HUN_HU_for pub | 28AUG2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Letter of Invitation_IRL_EN_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Master Tissue Brochure_FRA_FR_for pub | 28AUG2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_DEU_DE_for pub | 28AUG2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Flyer_DEU_DE_for pub | 28AUG2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Flyer_ESP_ES_for pub | 00 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Flyer_HUN_HU_for pub | 28AUG2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_DEU_DE_for pub | 28AUG2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_ESP_ES_for pub | 00 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_IRL_EN_for pub | 00 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Summary PIS_IRL_EN_for pub | 00b |
| Subject information and informed consent form (for publication) | L1_IC Main Consent_NOR_NN_for pub | 02FEB2023 |
| Subject information and informed consent form (for publication) | L1_ICF Optional_Tissue Sample_NOR_NN_for pub | 13OCT2022 |
| Subject information and informed consent form (for publication) | L1_ICF_Genetic consent_HUN_HU_for pub | 0.01 |
| Subject information and informed consent form (for publication) | L1_ICF_Genetic consent_PRT_PT_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main adult consent_FRA_FR_for pub | AM03v4.00R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_DEU_DE_for pub | AM2v2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_DNK_DA_for pub | AM02v2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_ESP_ES_SM05-RFI002_for pub | AM02v2-02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_HUN_HU_for pub | AM02v2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_IRL_EN_SM05_for pub | AM02_v2.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_ITA_IT_for pub | AM02v2.01 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_PRT_PT_for pub | AM02v2.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main data privacy_ITA_IT_for pub | 18JUL2022 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_add crossborder_DEU_DE_for pub | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_add reimbursement_DEU_DE_for pub | 2 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_DILI sample_ITA_IT_for pub | 18JUL2022 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnancy follow-up_IRL_EN_for pub | 00d |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnant partner_IRL_EN_for pub | 00d |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_right not to know_DNK_DA_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample data privacy_ITA_IT_for pub | 18JUL2022 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample_DEU_DE_for pub | 2 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample_ESP_ES_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample_FRA_FR_for pub | 2.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample_HUN_HU_for pub | 0.01 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample_IRL_EN_for pub | 00d |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample_ITA_IT_for pub | 0.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_stool sample_PRT_PT_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_DEU_DE_for pub | 3 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_DNK_DA_for pub | 1.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_ESP_ES_for pub | 1.01 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_FRA_FR_for pub | 2.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_HUN_HU_for pub | 1.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_IRL_EN_for pub | 1.02a |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_ITA_IT_for pub | v1.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_PRT_PT_for pub | AM01v1.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_withdrawal_ESP_ES_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_withdrawal_PRT_PT_for pub | 00 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-502116-36 _for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_ESP_ES_2022-502116-36-00_for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_FRA_FR_2022-502116-36 _for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_ITA_IT_2022-502116-36_for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_NOR_NN_for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_DEU_DE_for pub | 21APR2023 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_HUN_HU_for pub | 5-0 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_PRT_PT_2022-502116-36-00_for pub | 5R |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-05-19 | France | Acceptable 2023-07-27
|
2023-07-28 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-10-18 | France | Acceptable 2023-11-30
|
2023-11-30 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2023-12-20 | France | Acceptable 2024-03-06
|
2024-03-07 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-07-19 | France | Acceptable 2024-08-27
|
2024-08-27 |
| 5 | SUBSTANTIAL MODIFICATION | SM-5 | 2024-12-13 | France | Acceptable 2025-04-03
|
2025-04-03 |
| 6 | SUBSTANTIAL MODIFICATION | SM-11 | 2025-06-28 | France | Acceptable 2025-08-22
|
2025-08-22 |