Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ongoing, recruiting
Participants planned
495
Countries
6
Sites
16
Advanced Breast Cancer in older patients
The primary objective of the IMPORTANT study is to investigate the time to treatment failure (TTF) in vulnerable or frail older breast cancer patients treated with lower initial dose of CDK 4/6-inhibitors plus endocrine therapy compared to the recommended full dose of CDK 4/6-inhibitors.
Key facts
- Sponsor
- Region Oerebro Laen
- Participant type
- Patients
- Age range
- 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 25 Jan 2024 → ongoing
- Decision date (initial)
- 2023-11-28
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Project: 101104589 — IMPORTANT HORIZON-MISS-2022-CANCER-01
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacoeconomic, Efficacy, Safety, Therapy
The primary objective of the IMPORTANT study is to investigate the time to treatment failure (TTF) in vulnerable or frail older breast cancer patients treated with lower initial dose of CDK 4/6-inhibitors plus endocrine therapy compared to the recommended full dose of CDK 4/6-inhibitors.
Secondary objectives 7
- To compare the two treatment arms (lower initial dose of CDK 4/6-inhibitor vs. full dose) in terms of overall survival (OS)
- To compare the two treatment arms (lower initial dose of CDK 4/6-inhibitor vs. full dose) in terms of investigator-assessed progression-free survival (PFS).
- To compare the two treatment arms (lower initial dose of CDK 4/6-inhibitor vs. full dose) in terms of time to chemotherapy initiation.
- To compare the two treatment arms (lower initial dose of CDK 4/6-inhibitor vs. full dose) in terms of overall treatment utility (OTU; composite endpoint which integrates efficacy, tolerability, QoL and patient acceptability).
- To compare the two treatment arms (lower initial dose of CDK 4/6-inhibitor vs. full dose) in terms of treatment tolerability.
- To compare the two treatment arms (lower initial dose of CDK 4/6-inhibitor vs. full dose) in terms of patients’ quality of life (QoL).
- To compare the two treatment arms (lower initial dose of CDK 4/6-inhibitor vs. full dose) in terms of cost-effectiveness.
Conditions and MedDRA coding
Advanced Breast Cancer in older patients
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Patients male or female aged at least 65 years old at the time of informed consent. Male patients should use adequate contraceptive methods (e.g., double-barrier contraception) during therapy and for at least 14 weeks after completing therapy.
- Able to understand and consent in English language or in native language for each participating country.
- Histologically or cytologically confirmed diagnosis of HR-positive (defined as estrogen-receptor ≥ 1%), HER2-negative breast cancer according to analysis of the most recent tumor specimen by local laboratory.
- Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative treatment.
- No prior systemic treatment for advanced disease (recurrence during neo-/adjuvant endocrine therapy is allowed). A prior period of treatment with aromatase inhibitors or fulvestrant for up to 56 days from the CDK 4/6-inhibitor initiation is allowed as long as there is no disease progression during this time period.
- Adjuvant treatment with CDK4/6-inhibitors is allowed provided a disease-free interval from treatment end >12 months
- Written informed consent prior to any study-specific procedures.
- Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used including ECG for assessment of QT interval before treatment with ribociclib. Specifically, the following thresholds should be used to define adequate organ function: absolute neutrophil counts of ≥ 1,000/mm3, platelet counts of ≥ 100,000/mm3; ALT and/or AST ≤ 3 x upper limit normal (ULN), total bilirubin ≤ 2 x ULN; eGFR ≥ 30 mL/min.
- Able to swallow capsules.
Exclusion criteria 6
- Patients considered from treating physician as non-suitable for treatment with CDK 4/6-inhibitors.
- Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used.Specifically, any hypersensitivity to the active substance or to any of the excipients or to peanut, soya (for ribociclib) or use of preparations containing St. John’s Wort (for palbociclib) are contraindications.
- Presence of visceral crisis, lymphangitis carcinomatosis, or leptomeningeal carcinomatosis.
- History of any other cancer (except of non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
- Participating in other interventional trial.
- Patients with cognitive impairment (as assessed by treating physician) that preclude the ability to fill out the self-reported CGA.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Time to treatment failure
Secondary endpoints 8
- Overall Treatment Utility
- Overall survival
- Progression free survival
- Time to chemotherapy initiation
- Toxicity
- QoL
- Time to QoL deterioration
- Cost-effectiveness
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 7
Verzenios 50 mg film-coated tablets
PRD6701098 · Product
- Active substance
- Abemaciclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 540 g gram(s)
- Max treatment duration
- 60 Month(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
- No
Verzenios 150 mg film-coated tablets
PRD6705032 · Product
- Active substance
- Abemaciclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 540 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EF03 — -
- Marketing authorisation
- EU/1/18/1307/015
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Verzenios 100 mg film-coated tablets
PRD6701103 · Product
- Active substance
- Abemaciclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 540 g gram(s)
- Max treatment duration
- 60 Month(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
- No
PRD6503929 · Product
- Active substance
- Palbociclib
- Substance synonyms
- PD-332,991, PD-0332991
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 125 mg milligram(s)
- Max total dose
- 157.5 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EF01 — -
- Marketing authorisation
- EU/1/16/1147/001
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD6503996 · Product
- Active substance
- Palbociclib
- Substance synonyms
- PD-332,991, PD-0332991
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 125 mg milligram(s)
- Max total dose
- 157.5 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EF01 — -
- Marketing authorisation
- EU/1/16/1147/005
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD6520179 · Product
- Active substance
- Palbociclib
- Substance synonyms
- PD-332,991, PD-0332991
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 125 mg milligram(s)
- Max total dose
- 157.5 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EF01 — -
- Marketing authorisation
- EU/1/16/1147/003
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Kisqali 200 mg film-coated tablets
PRD5341538 · Product
- Active substance
- Ribociclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 600 mg milligram(s)
- Max total dose
- 756 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EF02 — -
- Marketing authorisation
- EU/1/17/1221/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 4
Femara 2,5 mg plėvele dengtos tabletės
PRD1928126 · Product
- Active substance
- Letrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 2.5 mg milligram(s)
- Max total dose
- 4.5 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BG04 — LETROZOLE
- Marketing authorisation
- LT/1/98/0128/002
- MA holder
- SIA NOVARTIS BALTICS
- MA country
- Lithuania
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Faslodex 250 mg solution for injection.
PRD3545736 · Product
- Active substance
- Fulvestrant
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 500 mg/ml milligram(s)/millilitre
- Max total dose
- 30 g/l gram(s)/litre
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BA03 — FULVESTRANT
- Marketing authorisation
- EU/1/03/269/002
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Arimidex® 1 mg film-coated tablets
PRD410197 · Product
- Active substance
- Anastrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 1 mg milligram(s)
- Max total dose
- 1.8 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BG03 — ANASTROZOLE
- Marketing authorisation
- PL 17901/0002
- MA holder
- ASTRAZENECA UK LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD1179828 · Product
- Active substance
- Exemestane
- Pharmaceutical form
- COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 45 g gram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BG06 — EXEMESTANE
- Marketing authorisation
- PA 822/111/1
- MA holder
- PFIZER HEALTHCARE IRELAND
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Region Oerebro Laen
- Sponsor organisation
- Region Oerebro Laen
- Address
- Sodra Grev Rosengatan
- City
- Orebro
- Postcode
- 701 85
- Country
- Sweden
Scientific contact point
- Organisation
- Region Oerebro Laen
- Contact name
- Assoc Prof Antonis Valachis
Public contact point
- Organisation
- Region Oerebro Laen
- Contact name
- Assoc Prof Antonis Valachis
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Phaze S.A. ORG-100047416
|
Athens, Greece | On site monitoring, Code 12, Code 5 |
Locations
6 EU/EEA countries · 16 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Finland | Ongoing, recruiting | 60 | 1 |
| Greece | Ongoing, recruiting | 95 | 9 |
| Italy | Ongoing, recruiting | 70 | 2 |
| Norway | Ongoing, recruiting | 60 | 1 |
| Spain | Ongoing, recruiting | 60 | 1 |
| Sweden | Ongoing, recruiting | 150 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
HUS Helsinki University Hospital
Department of Oncology, Comprehensive Cancer Center, Haartmaninkatu 4, 00290, Helsinki
General University Hospital Of Patras
Oncology Department, Rio, 265 04, Patras
Diagnostic & Therapeutic Center Of Athens Hygeia Single Member S.A.
3rd Department of Medical Oncology,, Erithrou Stavrou 4, 151 24, Maroussi
St. Luke's Hospital S.A.
Department of Medical Oncology, Harilaou Trikoupi Str. 3, 552 36, Thessaloniki
“Attikon” University General Hospital of Athens
2nd Propaedeutic Clinic of Internal Medicine, Oncology Unit, Rimini 1, Chaidari, athens
St Andrews Hospital
Medical Oncology Unit, Kalavriton 37, 26332, Patras
Theageneio Cancer Hospital
2nd Department of Medical Oncology, Simeonidi Alex 2, 546 39, Thessaloniki
HYGEIA Hospital
Second Department of Medical Oncology, 4, Erythrou Stavrou Str. & Kifisias Av., Athens
Metropolitan Hospital
Fourth Oncology Department & Comprehensive Clinical Trials Center, Ethnarchi Makariou 11, 185 47, Pireas
Metropolitan Hospital
2nd Department of Medical Oncology,, Ethnarchi Makariou 9, 185 47, Pireas
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 |
|---|---|---|---|---|---|
| Finland | 2024-04-09 | 2024-04-09 | |||
| Greece | 2024-12-20 | 2025-01-13 | |||
| Italy | 2025-02-04 | 2025-03-21 | |||
| Norway | 2024-04-16 | 2024-05-13 | |||
| Spain | 2024-04-29 | 2024-06-26 | |||
| Sweden | 2024-01-25 | 2024-04-25 |
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 2023-506620-87-00 | 5.0 |
| Protocol (for publication) | D1_ Protocol 2023-506620-87-00_GR | 5.0 |
| Protocol (for publication) | D1_ Protocol 2023-506620-87-00_GR_TC | 5.0 |
| Protocol (for publication) | D1_ Protocol 2023-506620-87-00_TC | 5.0 |
| Protocol (for publication) | D4_Patient facing documents CGA questionnaire IT | 1 |
| Protocol (for publication) | D4_Patient facing documents EQ-5D-5L questionnaire EN | n/a |
| Protocol (for publication) | D4_Patient facing documents EQ-5D-5L questionnaire SP | 1 |
| Protocol (for publication) | D4_Patient facing documents ICF EN | 6.0 |
| Protocol (for publication) | D4_Patient facing documents iMCQ questionnaire EN | n/a |
| Protocol (for publication) | D4_Patient facing documents iMCQ questionnaire SW | 1.0 |
| Protocol (for publication) | D4_Patient facing documents CGA questionnaire EN | n/a |
| Protocol (for publication) | D4_Patient facing documents CGA questionnaire GR | 1 |
| Protocol (for publication) | D4_Patient facing documents CGA questionnaire SP | 1.0 |
| Protocol (for publication) | D4_Patient facing documents CGA questionnaire SW | 1.0 |
| Protocol (for publication) | D4_Patient facing documents ELD14 questionnaire EN | n/a |
| Protocol (for publication) | D4_Patient facing documents ELD14 questionnaire GR | n/a |
| Protocol (for publication) | D4_Patient facing documents ELD14 questionnaire IT | n/a |
| Protocol (for publication) | D4_Patient facing documents ELD14 questionnaire SP | n/a |
| Protocol (for publication) | D4_Patient facing documents ELD14 questionnaire SW | n/a |
| Protocol (for publication) | D4_Patient facing documents EQ-5D-5L questionnaire GR | 1 |
| Protocol (for publication) | D4_Patient facing documents EQ-5D-5L questionnaire IT | 1 |
| Protocol (for publication) | D4_Patient facing documents EQ-5D-5L questionnaire SW | 1 |
| Protocol (for publication) | D4_Patient facing documents ICF EN_TCs | 6.0 |
| Protocol (for publication) | D4_Patient facing documents iMCQ_questionnaire GR | 1 |
| Protocol (for publication) | D4_Patient facing documents iMCQ_questionnaire SP | 1 |
| Protocol (for publication) | D4_Patient facing documents QLQ-C30 questionnaire EN | n/a |
| Protocol (for publication) | D4_Patient facing documents QLQ-C30 questionnaire GR | n/a |
| Protocol (for publication) | D4_Patient facing documents QLQ-C30 questionnaire IT | n/a |
| Protocol (for publication) | D4_Patient facing documents QLQ-C30 questionnaire SP | n/a |
| Protocol (for publication) | D4_Patient facing documents QLQ-C30 questionnaire SW | n/a |
| Protocol (for publication) | D4_Patient facing documents_Notification Letter for Participants_EN | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 2.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 3.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 3.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements_NO_TC | 2.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2.0 |
| Subject information and informed consent form (for publication) | ICF Privacy | 1 |
| Subject information and informed consent form (for publication) | ICF_Version 1 0_05mar2024_IT_FLO | 1 |
| Subject information and informed consent form (for publication) | ICF_Version 3_13dec2023_CA_TC | 3.0 |
| Subject information and informed consent form (for publication) | ICF_Version 3_13dec2023_ES_TC | 3.0 |
| Subject information and informed consent form (for publication) | ICF_Version 3_13dec2023_SW_TC | 3.0 |
| Subject information and informed consent form (for publication) | ICF_Version 5 0_02sep2024_GR_TC | 5.0 |
| Subject information and informed consent form (for publication) | Informativa medico_GP letter | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF SW | 5.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF SW_TC | 5.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_CA | 5.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_ES | 5.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_ES_TC | 5.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_FI | 6.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_FI_TC | 6.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_IT_IT | 6.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_IT_TC | 6.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_NO | 6.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_NO_C | 6.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_GR | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_GR_C | 7.0 |
| Subject information and informed consent form (for publication) | Notification Letter for Participants ES | 1 |
| Subject information and informed consent form (for publication) | Notification Letter for Participants_GR | 1 |
| Subject information and informed consent form (for publication) | Notification Letter for Participants_IT | 1 |
| Subject information and informed consent form (for publication) | Notification Letter for Participants_SW | 1 |
| Subject information and informed consent form (for publication) | Notification Letter to Participants CA | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC Verzenios | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Ibrance | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Kisqali | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_EN 2023 506620 87 00 | 5.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_GR 2023 506620 87 00 | 5.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_IT 2023 506620 87 00 | 5.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_IT 2023 506620 87 00_TC | 5.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_NO 2023 506620 87 00 | 5.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_SP 2023 506620 87 00 | 5.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_SW 2023 506620 87 00 | 5.0 |
Application history
11 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-08-04 | Sweden | Acceptable with conditions 2023-11-27
|
2023-11-27 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2023-12-08 | Acceptable with conditions 2023-11-27
|
2023-12-08 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-01-03 | Sweden | Acceptable 2024-02-19
|
2024-02-19 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2024-02-29 | Acceptable 2024-02-19
|
2024-02-29 | |
| 5 | SUBSEQUENT ADDITION OF MSC | APP-5 | 2024-03-12 | 2024-06-06 | ||
| 6 | SUBSEQUENT ADDITION OF MSC | APP-6 | 2024-06-11 | 2024-09-09 | ||
| 7 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-06-11 | Acceptable with conditions | 2024-08-29 | |
| 8 | SUBSTANTIAL MODIFICATION | SM-8 | 2024-09-25 | Acceptable with conditions | 2024-11-11 | |
| 9 | SUBSTANTIAL MODIFICATION | SM-9 | 2024-12-17 | Sweden | Acceptable 2025-04-11
|
2025-04-14 |
| 10 | SUBSTANTIAL MODIFICATION | SM-12 | 2025-05-26 | Acceptable | 2025-07-10 | |
| 11 | SUBSTANTIAL MODIFICATION | SM-13 | 2025-12-26 | Sweden | Acceptable 2026-03-09
|
2026-03-09 |