(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

NCT05208047 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CGT9486-21-301
• Study Type: interventional
• Target: 482
• Locations: 22 countries
• Sites: 126

Brief Summary

This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 482 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for Gastrointestinal Stromal Tumors (GIST) and 2) evaluating the potential for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner. This study also contains two substudies: 1) a drug-drug interactions (DDI) substudy will investigate the potential for CGT9486 to be a Cytochrome P450 (CYP)3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST and 2) a substudy intended to test the efficacy of bezuclastinib and sunitinib as first-line (1L) treatment of GIST in approximately 40 participants with KIT exon 9 mutations and no prior systemic therapy (with the exception of up to 10 subjects with ongoing imatinib therapy of ≤4 weeks).

Conditions

Advanced Gastrointestinal Stromal Tumors; Metastatic Cancer

Keywords

Sunitinib; Solid Tumors; Gastrointestinal Stromal Tumors; Gastrointestinal; KIT; Kinase Inhibitors; Growth Inhibitors; CGT9486; Unresectable; Metastatic; GIST; Bezuclastinib; PLX9486; Midazolam; Drug-drug interaction

Outcome Measures

Primary Outcomes (8)

• Part 1a - pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax)

  16 days

• Part 1a - pharmacokinetics - AUC

  Area under the plasma concentration-time curve (AUC)

  16 days

• Part 1b - pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax)

  14 days

• Part 1b - pharmacokinetics - AUC

  Area under the plasma concentration-time curve (AUC)

  14 days

• Part 1b - pharmacokinetics - Tmax

  Time to maximum observed plasma concentration (Tmax)

  14 days

• Part 2 - Progression Free Survival (PFS)

  Time from first dose to documented disease progression or death due to any cause, whichever occurs first

  Approximately 48 months

• DDI Substudy - pharmacokinetics - AUC

  Area under the plasma concentration-time curve (AUC)

  16 days

• DDI Substudy - pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax)

  14 days

Secondary Outcomes (10)

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• Part 1a, Part 1b, Part 2 - Overall Survival (OS)

  Approximately 48 months

Study Arms (7)

Part 1a

EXPERIMENTAL

CGT9486 plus sunitinib 37.5 mg QD

Drug: CGT9486; Drug: Sunitinib

Part 2 - Experimental Group

EXPERIMENTAL

CGT9486 plus sunitinib 37.5 mg QD

Drug: CGT9486; Drug: Sunitinib

Part 2 - Control Group

ACTIVE COMPARATOR

sunitinib 37.5 mg QD

Drug: Sunitinib

Part 1b - DDI Cohort 1

EXPERIMENTAL

CGT9486 plus sunitinib 37.5 mg QD

Drug: CGT9486; Drug: Sunitinib

Part 1b - DDI Cohort 2

EXPERIMENTAL

sunitinib 37.5 mg QD plus CGT9486

Drug: Sunitinib; Drug: CGT9486

DDI Substudy (Midazolam)

EXPERIMENTAL

Midazolam, CGT9486, sunitinib

Drug: Midazolam; Drug: CGT9486; Drug: Sunitinib

GIST 1L Substudy

EXPERIMENTAL

CGT9486, sunitinib

Drug: CGT9486; Drug: Sunitinib

Interventions

Midazolam DRUG

Participants will receive a single-dose of midazolam on Day 1 and Day 16

DDI Substudy (Midazolam)

Sunitinib DRUG

Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

Part 1b - DDI Cohort 2

CGT9486 DRUG

Participants will receive CGT9486 orally until study stopping rules are met.

Also known as: Bezuclastinib

GIST 1L Substudy; Part 1a; Part 2 - Experimental Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization. (GIST 1L Substudy: must have documented mutation in KIT Exon 9 with an available molecular pathology report; archival or fresh tumor tissue sample will be required)
• Documented disease progression on or intolerance to imatinib (Part 1a, Part 1b, Part 2, DDI Substudy)
• Subjects must have received the following treatment:
• DDI Substudy/Part 1a: Treatment with ≥1 prior lines of therapy for GIST
• Part 1b: Treatment with ≥2 prior TKI for GISTs
• Part 2: Prior treatment with imatinib only
• GIST 1L Substudy: No prior systemic therapy for GIST including adjuvant therapy. Exception: up to 10 subjects with ongoing imatinib therapy of ≤4 weeks
• Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2, GIST 1L Substudy)
• Eastern Cooperative Oncology Group (ECOG) Status
• to 2 (Part 1a, Part 1b, Part 2, DDI Substudy)
• to 1 (GIST 1L Substudy)
• Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

You may not qualify if:

• Known Platelet-Derived Growth Factor Receptor (PDGFR) driving mutations or known succinate dehydrogenase deficiency (Part 1a, Part 1b, Part 2, DDI Substudy)
• Clinically significant cardiac disease
• Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug (Part 1a, Part 1b, Part 2, DDI Substudy)
• Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
• Any active bleeding excluding hemorrhoidal or gum bleeding
• Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody.
• Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
• Received strong CYP3A4 inhibitors or inducers (Part 1a, Part 1b, Part 2, DDI Substudy)
• Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (126)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

WITHDRAWN

Mayo Clinic

Scottsdale, Arizona, 85259, United States

ACTIVE NOT RECRUITING

University of Arizona- Cancer Center

Tucson, Arizona, 85719, United States

ACTIVE NOT RECRUITING

City of Hope

Duarte, California, 91010, United States

ACTIVE NOT RECRUITING

University of California, Los Angeles (UCLA)

Los Angeles, California, 90404, United States

ACTIVE NOT RECRUITING

University of California, San Diego (UCSD)

San Diego, California, 92093, United States

ACTIVE NOT RECRUITING

University of California, San Francisco

San Francisco, California, 94158, United States

ACTIVE NOT RECRUITING

University of Colorado Denver

Denver, Colorado, 80204, United States

ACTIVE NOT RECRUITING

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

ACTIVE NOT RECRUITING

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Mid Florida Hematology and Oncology Center

Orange City, Florida, 32763, United States

WITHDRAWN

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

ACTIVE NOT RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

ACTIVE NOT RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

ACTIVE NOT RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Washington University

St Louis, Missouri, 63130, United States

RECRUITING

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

ACTIVE NOT RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

ACTIVE NOT RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

ACTIVE NOT RECRUITING

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

WITHDRAWN

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

ACTIVE NOT RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

ACTIVE NOT RECRUITING

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

ACTIVE NOT RECRUITING

University of Tennessee

Knoxville, Tennessee, 37920, United States

WITHDRAWN

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

ACTIVE NOT RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

ACTIVE NOT RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

ACTIVE NOT RECRUITING

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, 53705, United States

ACTIVE NOT RECRUITING

Instituto Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

ACTIVE NOT RECRUITING

Instituto Oncologico de Cordoba (IONC)

Córdoba, X5000HWE, Argentina

ACTIVE NOT RECRUITING

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

ACTIVE NOT RECRUITING

Bankstown-Lidcombe Hospital

Bankstown, 2200, Australia

ACTIVE NOT RECRUITING

Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)

Campinas, 130.83-888, Brazil

ACTIVE NOT RECRUITING

lnstituto Nacional de Cancer - INCA

Rio de Janeiro, 20.230-130, Brazil

ACTIVE NOT RECRUITING

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

São Paulo, 09060-650, Brazil

ACTIVE NOT RECRUITING

Alberta Health Services Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

ACTIVE NOT RECRUITING

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

ACTIVE NOT RECRUITING

Tom Baker Cancer Center

Calgary, T2N 4N2, Canada

ACTIVE NOT RECRUITING

Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)

Montreal, HIT 2M4, Canada

ACTIVE NOT RECRUITING

Instituto Oncologico FALP

Santiago, 7500921, Chile

ACTIVE NOT RECRUITING

Centro de Oncologia de Precision, Universidad Mayor

Santiago, 7560908, Chile

ACTIVE NOT RECRUITING

Masarykuv onkologicky ustav

Brno, 65653, Czechia

ACTIVE NOT RECRUITING

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

WITHDRAWN

Fakultni nemocnice Olomouc - Oncology clinic

Olomouc, 77900, Czechia

ACTIVE NOT RECRUITING

Aarhus University Hospital

Aarhus, 8200, Denmark

ACTIVE NOT RECRUITING

Institut Bergonie

Bordeaux, 33076, France

ACTIVE NOT RECRUITING

Centre Oscar Lambret

Lille, 59000, France

ACTIVE NOT RECRUITING

Centre Leon Berard

Lyon, 69008, France

ACTIVE NOT RECRUITING

AP-HM - Hôpital de la Timone

Marseille, 13005, France

ACTIVE NOT RECRUITING

Centre Eugene Marquis

Rennes, 35042, France

ACTIVE NOT RECRUITING

ICO St-Herblain

Saint-Herblain, 44800, France

ACTIVE NOT RECRUITING

CHU de Toulouse - Hospital Rangueil

Toulouse, 31400, France

ACTIVE NOT RECRUITING

Gustave Roussy

Villejuif, 94805, France

ACTIVE NOT RECRUITING

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

ACTIVE NOT RECRUITING

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

ACTIVE NOT RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

ACTIVE NOT RECRUITING

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

ACTIVE NOT RECRUITING

Medizinische Hochschule Hannover- Urology Oncology

Hanover, 30625, Germany

ACTIVE NOT RECRUITING

Universitaetsmedizin Mannheim

Mannheim, 68167, Germany

ACTIVE NOT RECRUITING

Humanity & Health Clinical Trial Centre

Central, Hong Kong

WITHDRAWN

Hong Kong United Oncology Centre

Jordon, Hong Kong

ACTIVE NOT RECRUITING

Prince of Wales Hospital

Shatin, Hong Kong

ACTIVE NOT RECRUITING

Debreceni Egyetem, Klinikai Központ, Onkológiai Klinika

Debrecen, 4032, Hungary

ACTIVE NOT RECRUITING

Centro Riferimento Oncologico - Aviano

Aviano, 33081, Italy

ACTIVE NOT RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna, 40138, Italy

ACTIVE NOT RECRUITING

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

ACTIVE NOT RECRUITING

IRCCS La Fondazione e l'Istituto di Candiolo

Candiolo, 10060, Italy

WITHDRAWN

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

ACTIVE NOT RECRUITING

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"

Meldola, 47014, Italy

ACTIVE NOT RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

ACTIVE NOT RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

ACTIVE NOT RECRUITING

Policlinico Universitario Campus Bio-Medico

Roma, 00128, Italy

ACTIVE NOT RECRUITING

Istituto Clinico Humanitas

Rozzano, 20089, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento

Verona, 31726, Italy

ACTIVE NOT RECRUITING

Centro de Investigacion Medica Aquascalientes (CIMA)

Aguascalientes, 20116, Mexico

WITHDRAWN

I Can Oncology Center SA De CV

Monterrey, 64710, Mexico

ACTIVE NOT RECRUITING

Oaxaca Site Management Organization S.C.

Oaxaca City, 68000, Mexico

WITHDRAWN

Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)

Amsterdam, 1066 CX, Netherlands

ACTIVE NOT RECRUITING

UMC Groningen

Groningen, 9713 GZ, Netherlands

ACTIVE NOT RECRUITING

Stichting Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

ACTIVE NOT RECRUITING

Erasmus MC

Rotterdam, 3015 GD, Netherlands

ACTIVE NOT RECRUITING

Haukeland University Hospital - Bergen

Bergen, 5021, Norway

ACTIVE NOT RECRUITING

Oslo University Hospital

Oslo, 0310, Norway

ACTIVE NOT RECRUITING

Szpital Specjalistyczny w Brzozowie

Brzozów, 36-200, Poland

ACTIVE NOT RECRUITING

Centrum Onkologii im. Prof. Franciszka Lukaszczyka

Bydgoszcz, 85-796, Poland

WITHDRAWN

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, Oddzial Chemioterapii Dziennej

Gliwice, 44-102, Poland

ACTIVE NOT RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow

Warsaw, 02-781, Poland

ACTIVE NOT RECRUITING

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

WITHDRAWN

Seoul National University Hosptial

Seoul, 03080, South Korea

ACTIVE NOT RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

ACTIVE NOT RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

ACTIVE NOT RECRUITING

Korea University Guro Hospital

Seoul, 08308, South Korea

ACTIVE NOT RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

ACTIVE NOT RECRUITING

Hospital de la Santa Creu i Sant Pau Barcelona

Barcelona, 08041, Spain

WITHDRAWN

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, 08908, Spain

ACTIVE NOT RECRUITING

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar, 30120, Spain

WITHDRAWN

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

ACTIVE NOT RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

ACTIVE NOT RECRUITING

Hospital Fundación Jiménez Díaz

Madrid, 28040, Spain

ACTIVE NOT RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

ACTIVE NOT RECRUITING

Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

WITHDRAWN

Skane University Hospital Lund

Lund, 22185, Sweden

ACTIVE NOT RECRUITING

Karolinska University Hospital

Solna, 171 76, Sweden

ACTIVE NOT RECRUITING

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung City, 83301, Taiwan

ACTIVE NOT RECRUITING

National Taiwan University Hospital

New Taipei City, 10002, Taiwan

ACTIVE NOT RECRUITING

China Medical University Hospital

Taichung, 40447, Taiwan

ACTIVE NOT RECRUITING

Taipei Veterans General Hospital (VGHTP)

Taipei, 11217, Taiwan

ACTIVE NOT RECRUITING

Chang Gung Memorial Hospital - Linkou Branch (CGMHLK)

Taoyuan, 33305, Taiwan

ACTIVE NOT RECRUITING

Cambridge Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

ACTIVE NOT RECRUITING

Beatson, West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

WITHDRAWN

University College London Hospital

London, NW1 2PG, United Kingdom

ACTIVE NOT RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

WITHDRAWN

Royal Marsden Hospital - Surrey

London, SW3 6JJ, United Kingdom

ACTIVE NOT RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

ACTIVE NOT RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2SJ, United Kingdom

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Gastrointestinal Stromal Tumors

Interventions

Sunitinib; Midazolam

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines

Central Study Contacts

Cogent Biosciences

CONTACT

617-945-5576; peakinfo@cogentbio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-part study: Part 1a is a single-arm design, Part 1b is a two-arm parallel design drug-drug interaction evaluation in the first treatment cycle and single-arm design in subsequent treatment cycles, and Part 2 is a randomized two-arm parallel comparator study. The DDI substudy is a single-arm, fixed-sequence, crossover design to investigate the potential for CGT9486 to be a CYP3A4 inducer. The GIST 1L substudy is a single-arm study of bezuclastinib+sunitinib exploring efficacy in a 1L setting.

Study Record Dates

• First Submitted: December 23, 2021
• First Posted: January 26, 2022
• Study Start: April 14, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): January 1, 2030
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (7); US (36); FR (8); DE (6); CZ (3); NO (2); BR (3); ES (11); DK (1); NL (4); PL (4); TW (5); CL (2); CA (4); ME (3); HK (3); HU (1); IT (12); AR (2); KR (5); AU (2); SE (2)