Study of Olaparib (MK-7339) in Combination With Pembrolizumab (MK-3475) in the Treatment of Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer (MK-7339-007/KEYLYNK-007)

NCT04123366 | Active Not Recruiting Phase 2 FDA Drug

• 7 other identifiers: 7339-007MK-7339-007KEYLYNK-007jRCT20112000252023-503831-17-00U1111-1288-16422019-001745-40
• Study Type: interventional
• Target: 300
• Locations: 23 countries
• Sites: 135

Brief Summary

The purpose of this study is to assess the efficacy and safety of treatment with olaparib (MK-7339) in combination with pembrolizumab (MK-3475) in adults with previously treated, advanced (metastatic and/or unresectable) Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-positive solid tumors.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 in Biomarker Subgroups

  ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The ORR for all participants will be presented by biomarker subgroup.

  Up to ~3 years

Secondary Outcomes (12)

• Duration of Response (DOR) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups

  Up to ~3 years

• Progression-Free Survival (PFS) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups

  Up to ~3 years

• Overall Survival (OS) in Biomarker Subgroups

  Up to ~3 years

• Number of Participants Who Experience an Adverse Event (AE)

  Up to ~3 years

• Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

  Up to ~3 years

Study Arms (1)

Olaparib+Pembrolizumab

EXPERIMENTAL

Participants receive olaparib 300 mg via oral tablet 2 times each day PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 21-day cycle. Participants may receive olaparib+pembrolizumab for up to approximately 2 years.

Drug: Olaparib; Biological: Pembrolizumab

Interventions

Olaparib DRUG

Oral tablet

Also known as: MK-7339, LYNPARZA®

Olaparib+Pembrolizumab

Pembrolizumab BIOLOGICAL

Intravenous infusion

Also known as: MK-3475, KEYTRUDA®

Olaparib+Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline or somatic BRCA mutation) that is not eligible for curative treatment and for which standard of care therapy has failed. Participants must have progressed on or be intolerant to standard of care therapies that are known to provide clinical benefit. There is no limit on the number of prior treatment regimens.
• Has either centrally-confirmed known or suspected deleterious mutations in ≥1 of the specified 15 genes involved in HRR or centrally-confirmed HRD based on the Lynparza HRR-HRD assay.
• Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology and confirmed in real time by blinded independent central review (BICR). BICR must confirm the presence of radiologically measurable disease per RECIST 1.1 for the participant to be eligible for the study.
• Has a life expectancy of ≥3 months.
• Must have had CR or PR while on the last treatment with prior cisplatin or carboplatin, or if received only oxaliplatin had CR, PR, or stable disease (SD) while on the last treatment with prior oxaliplatin (either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor. Participant must also not have been refractory to prior platinum-containing therapy.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of study treatment initiation.
• Male participants must agree to use contraception during the treatment period and for ≥90 days (3 months) after the last dose of olaparib and refrain from donating sperm during this period.
• Female participants must not be pregnant or breastfeeding, and ≥1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP who agrees to use contraception during the treatment period and for ≥120 days (3 months) after the last dose of pembrolizumab and 180 days (6 months) after the last dose of olaparib, has a highly sensitive pregnancy test within 24 hours for urine or within 72 hours for serum before the first dose of study intervention, and abstains from breastfeeding during the study intervention period and for at least 120 days after the last dose of the study intervention.
• Has adequate organ function

You may not qualify if:

• Has a known additional malignancy that is progressing or has required active treatment in the last 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded.
• Has a history of non-infectious pneumonitis/interstitial lung disease that required treatment with steroids or currently has pneumonitis/interstitial lung disease.
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has an active infection requiring systemic therapy.
• Has active tuberculosis (Bacillus tuberculosis \[TB\]).
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing \>10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Has received colony-stimulating factors (e.g. granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\] or recombinant erythropoietin) within 28 days prior to the first dose of study treatment.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active hepatitis B or hepatitis C.
• Is unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption).
• Has received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-programmed death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX 40 \[Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)\], CD137 \[tumor necrosis factor receptor superfamily member 9 (TNFRSF9)\]).
• Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (poly\[ADP ribose\]) polymerization (PARP) inhibitor.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to administration of study treatment.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (135)

The Kirklin Clinic ( Site 0086)

Birmingham, Alabama, 35233, United States

Location

Banner MD Anderson Cancer Center ( Site 0049)

Gilbert, Arizona, 85234, United States

Location

UC Davis Comprehensive Cancer Center ( Site 0039)

Sacramento, California, 95817, United States

Location

San Francisco Oncology Associates ( Site 0085)

San Francisco, California, 94115, United States

Location

University of California San Francisco ( Site 0015)

San Francisco, California, 94158, United States

Location

Banner MD Anderson Cancer Center ( Site 0092)

Greeley, Colorado, 80631, United States

Location

University of Florida ( Site 0078)

Gainesville, Florida, 32608, United States

Location

Winship Cancer Institute of Emory University ( Site 0057)

Atlanta, Georgia, 30322, United States

Location

Northeast Georgia Medical Center ( Site 0026)

Gainesville, Georgia, 30501, United States

Location

Northwest Georgia Oncology Centers PC ( Site 0047)

Marietta, Georgia, 30060, United States

Location

Norton Cancer Institute - St. Matthews ( Site 0024)

Louisville, Kentucky, 40207, United States

Location

Atlantic Health System ( Site 0046)

Summit, New Jersey, 07901, United States

Location

New York Cancer and Blood Specialists-Research Department ( Site 0080)

Port Jefferson Station, New York, 11776, United States

Location

University Hospitals Cleveland Medical Center ( Site 0016)

Cleveland, Ohio, 44106, United States

Location

The University of Oklahoma Health Sciences Center ( Site 0050)

Oklahoma City, Oklahoma, 73104, United States

Location

Parkland Health & Hospital System ( Site 0091)

Dallas, Texas, 75235, United States

Location

University of Texas, Southwestern Medical Center ( Site 0004)

Dallas, Texas, 75390, United States

Location

University of Texas-MD Anderson Cancer Center ( Site 0087)

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists ( Site 0038)

West Valley City, Utah, 84119, United States

Location

Inova Schar Cancer Institute ( Site 0008)

Fairfax, Virginia, 22031, United States

Location

Northwest Medical Specialties, PLLC ( Site 0007)

Tacoma, Washington, 98405, United States

Location

Fundacion CIDEA ( Site 2704)

Ciudad de Buenos Aires, Buenos Aires F.D., C1121ABE, Argentina

Location

Hospital Britanico de Buenos Aires ( Site 2705)

Ciudad de Buenos Aires, Buenos Aires F.D., C1280AEB, Argentina

Location

Centro Medico Dra De Salvo ( Site 2702)

Buenos Aires, C1426ABP, Argentina

Location

CEMIC ( Site 2701)

Buenos Aires, C1431FWO, Argentina

Location

Centro Oncologico Riojano Integral ( Site 2703)

La Rioja, F5300COE, Argentina

Location

Blacktown Hospital ( Site 2202)

Blacktown, New South Wales, 2148, Australia

Location

Tasman Oncology Research Pty Ltd ( Site 2203)

Southport, Queensland, 4215, Australia

Location

Monash Medical Centre ( Site 2205)

Clayton, Victoria, 3168, Australia

Location

Linear Clinical Research Ltd ( Site 2206)

Nedlands, Western Australia, 6009, Australia

Location

BC Cancer-Vancouver Center ( Site 0203)

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Moncton Hospital - Horizon Health Network ( Site 0206)

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0201)

Montreal, Quebec, H2X 1R9, Canada

Location

Fundación Colombiana de Cancerología Clínica Vida ( Site 2902)

Medellín, Antioquia, 050030, Colombia

Location

Clinica de la Costa S.A.S. ( Site 2900)

Barranquilla, Atlántico, 080020, Colombia

Location

Fundacion Cardiovascular de Colombia ( Site 2907)

Piedecuesta, Santander Department, 68017, Colombia

Location

Hemato Oncologos S.A. ( Site 2910)

Cali, Valle del Cauca Department, 76001, Colombia

Location

Fundacion Valle del Lili ( Site 2909)

Cali, Valle del Cauca Department, 760032, Colombia

Location

CHU Jean Minjoz ( Site 0606)

Besançon, Doubs, 25030, France

Location

Institut du Cancer de Montpellier ( Site 0610)

Montpellier, Herault, 34298, France

Location

Centre Henri Becquerel ( Site 0607)

Rouen, Seine-Maritime, 76038, France

Location

Institut Gustave Roussy ( Site 0602)

Villejuif, Val-de-Marne, 94800, France

Location

CHD Vendee ( Site 0604)

La Roche-sur-Yon, Vendee, 85925, France

Location

Universitaetsklinik der Ludwig-Maximilians-Universitaet Muenchen ( Site 0906)

Munich, Bavaria, 81377, Germany

Location

Universitaetsklinik Koeln ( Site 0903)

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Charite-Universitaetsmedizin Berlin-Campus Benjamin Franklin ( Site 0902)

Berlin, 12203, Germany

Location

Oncologika S.A. ( Site 3003)

Guatemala City, 01010, Guatemala

Location

Grupo Angeles SA ( Site 3004)

Guatemala City, 01015, Guatemala

Location

Sanatorio Nuestra Senora del Pilar ( Site 3006)

Guatemala City, 01015, Guatemala

Location

Medi-K Cayala ( Site 3005)

Guatemala City, 01016, Guatemala

Location

Centro Medico Integral De Cancerología (CEMIC) ( Site 3002)

Quetzaltenango, 09002, Guatemala

Location

Rambam Health Care Campus-Oncology Division ( Site 0801)

Haifa, 3109601, Israel

Location

Hadassah Ein Kerem Medical Center ( Site 0802)

Jerusalem, 9112001, Israel

Location

Meir Medical Center ( Site 0804)

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center ( Site 0806)

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center ( Site 0800)

Ramat Gan, 5262000, Israel

Location

Sourasky Medical Center ( Site 0805)

Tel Aviv, 6423906, Israel

Location

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0703)

Modena, Emilia-Romagna, 41124, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda ( Site 0700)

Milan, 20162, Italy

Location

Istituto Nazionale Tumori Fondazione Pascale ( Site 0705)

Naples, 80131, Italy

Location

Azienda Ospedaliera Universitaria Senese ( Site 0704)

Siena, 53100, Italy

Location

Aichi Cancer Center Hospital ( Site 2504)

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East ( Site 2500)

Kashiwa, Chiba, 277-8577, Japan

Location

Hokkaido University Hospital ( Site 2502)

Sapporo, Hokkaido, 060-8648, Japan

Location

Kyushu University Hospital ( Site 2506)

Fukuoka, 812-8582, Japan

Location

Okayama University Hospital ( Site 2505)

Okayama, 700-8558, Japan

Location

National Cancer Center Hospital ( Site 2501)

Tokyo, 104-0045, Japan

Location

Japanese Foundation for Cancer Research ( Site 2503)

Tokyo, 135-8550, Japan

Location

Daugavpils Regional Hospital ( Site 2104)

Daugavpils, 5417, Latvia

Location

Liepaja Regional Hospital ( Site 2101)

Liepāja, 3414, Latvia

Location

Riga East Clinical University Hospital ( Site 2103)

Riga, 1079, Latvia

Location

P. Stradina Clinical University Hospital ( Site 2102)

Riga, LV-1002, Latvia

Location

Preparaciones Oncologicas ( Site 3102)

León, Guanajuato, 37178, Mexico

Location

Unidad Biomedica Avanzada Monterrey S. A. ( Site 3108)

Monterrey, Nuevo León, 64460, Mexico

Location

Centro Medico Zambrano Hellion ( Site 3105)

San Pedro Garza García, Nuevo León, 66278, Mexico

Location

Hospital H+ Queretaro ( Site 3104)

Querétaro City, Querétaro, 76000, Mexico

Location

Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 3101)

Madero, Tamaulipas, 89440, Mexico

Location

CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 3103)

Mexico City, 06100, Mexico

Location

Clinica Integral Internacional de Oncologia S. de R.L. de C.V. ( Site 3107)

Puebla City, 72530, Mexico

Location

Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 3206)

Arequipa, Ariqipa, 04001, Peru

Location

Hospital Nacional Daniel Alcides Carrion ( Site 3207)

Bellavista, Qallaw, 07021, Peru

Location

Hospital Nacional Adolfo Guevara Velasco ( Site 3205)

Cuzco, Qusqu, 08003, Peru

Location

Oncosalud ( Site 3200)

Lima, 15036, Peru

Location

Instituto Nacional de Enfermedades Neoplasicas ( Site 3201)

Lima, 15038, Peru

Location

Hospital Nacional Arzobispo Loayza ( Site 3208)

Lima, 15082, Peru

Location

Clinica San Gabriel ( Site 3202)

Lima, 15088, Peru

Location

Hospital Nacional Cayetano Heredia ( Site 3203)

Lima, 15102, Peru

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Uniwersyteckie Centrum Kliniczne ( Site 1809)

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Hematology and Oncology Institute ( Site 0504)

Manati, 00674, Puerto Rico

Location

Ad-Vance Medical Research LLC ( Site 0505)

Ponce, 00717, Puerto Rico

Location

Pan American Center for Oncology Trials LLC ( Site 0501)

Rio Piedras, 00935, Puerto Rico

Location

FDI Clinical Research ( Site 0500)

San Juan, 00927, Puerto Rico

Location

Spitalul Judetean de Urgenta Alba Iulia ( Site 1107)

Alba Iulia, Alba, 510007, Romania

Location

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1101)

Cluj-Napoca, Cluj, 400015, Romania

Location

Medisprof ( Site 1102)

Cluj-Napoca, Cluj, 400641, Romania

Location

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1103)

Craiova, Dolj, 200542, Romania

Location

Policlinica Oncomed SRL ( Site 1104)

Timișoara, Timiș County, 300239, Romania

Location

Universitas Annex National Hospital ( Site 1902)

Bloemfontein, Free State, 9301, South Africa

Location

Wits Clinical Research ( Site 1906)

Parktown-Johannesburg, Gauteng, 2193, South Africa

Location

Mary Potter Oncology Centre, Little Company of Mary Hospital ( Site 1900)

Pretoria, Gauteng, 0181, South Africa

Location

Vaal Triangle Oncology Centre ( Site 1905)

Vereeniging, Gauteng, 1930, South Africa

Location

The Oncology Centre ( Site 1904)

Durban, KwaZulu-Natal, 4091, South Africa

Location

Cancercare Rondebosch Oncology ( Site 1901)

Rondebosch, Western Cape, 7700, South Africa

Location

Seoul National University Bundang Hospital ( Site 2403)

Seongnam-si, Kyonggi-do, 13605, South Korea

Location

Seoul National University Hospital ( Site 2402)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 2400)

Seoul, 03722, South Korea

Location

Samsung Medical Center ( Site 2401)

Seoul, 06351, South Korea

Location

Hospital Quiron de Madrid ( Site 1301)

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Clinic i Provincial ( Site 1302)

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon ( Site 1300)

Madrid, 28007, Spain

Location

Skanes Universitetssjukhus Lund. ( Site 2001)

Lund, Skåne County, 221 85, Sweden

Location

Karolinska Universitetssjukhuset Solna ( Site 2000)

Solna, Stockholm County, 171 76, Sweden

Location

Akademiska Sjukhuset ( Site 2002)

Uppsala, Uppsala County, 751 85, Sweden

Location

Baskent University Adana Training Hospital ( Site 1509)

Adana, 01250, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1502)

Ankara, 06100, Turkey (Türkiye)

Location

Gazi Universitesi Tip Fakultesi ( Site 1507)

Ankara, 06500, Turkey (Türkiye)

Location

Ankara Sehir Hastanesi ( Site 1508)

Ankara, 06800, Turkey (Türkiye)

Location

Akdeniz Universitesi Tıp Fakultesi ( Site 1503)

Antalya, 07070, Turkey (Türkiye)

Location

Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1500)

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1504)

Istanbul, 34098, Turkey (Türkiye)

Location

Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi ( Site 1505)

Istanbul, 34722, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi ( Site 1501)

Izmir, 35040, Turkey (Türkiye)

Location

Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1510)

Konya, 42080, Turkey (Türkiye)

Location

Inonu Universitesi Medical Fakultesi ( Site 1506)

Malatya, 44280, Turkey (Türkiye)

Location

Cherkasy Regional Oncology Dispensary ( Site 1702)

Cherkasy, Cherkasy Oblast, 18009, Ukraine

Location

Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council ( Site 1700)

Dnipro, Dnipropetrovsk Oblast, 49102, Ukraine

Location

Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Department for daily treated patient (

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine

Location

Communal non profit enterprise Regional Clinical Oncology Center ( Site 1704)

Kharkiv, Kharkivs’ka Oblast’, 61070, Ukraine

Location

Khmelnitskiy Regional Onkology Dispensary ( Site 1705)

Khmelnitskiy, Khmelnytskyi Oblast, 29009, Ukraine

Location

Kirovograd Regional oncology Dispensary ( Site 1716)

Kropyvnytsky, Kirovohrad Oblast, 25011, Ukraine

Location

Medical Centre Consilium Medical ( Site 1712)

Kyiv, Kyivska Oblast, 04050, Ukraine

Location

Podillya Regional Center of Oncology ( Site 1708)

Vinnytsia, Vinnytsia Oblast, 21029, Ukraine

Location

Medical center of the Limited Liability Company Yulis ( Site 1714)

Zaporizhzhia, Zaporizhzhia Oblast, 69035, Ukraine

Location

Zhytomyr Regional Oncology Center ( Site 1710)

Zhytomyr, Zhytomyr Oblast, 10002, Ukraine

Location

Related Publications (1)

• Cannon TL, Randall JN BA, Sokol ES, Alexander SM, Wadlow RC, Winer AA, Barnett DM, Rayes DL BS, Nimeiri HS, McGregor KA. Concurrent BRAFV600E and BRCA Mutations in MSS Metastatic Colorectal Cancer: Prevalence and Case Series of mCRC patients with prolonged OS. Cancer Treat Res Commun. 2022;32:100569. doi: 10.1016/j.ctarc.2022.100569. Epub 2022 Apr 30.

  PMID: 35567913 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

olaparib; pembrolizumab

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 10, 2019
• Study Start: November 18, 2019
• Primary Completion (Estimated): June 29, 2026
• Study Completion (Estimated): June 29, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AR (5); LA (4); PL (2); IL (6); KR (4); DE (3); ME (7); PR (4); PE (8); JP (7); FR (5); SE (3); GU (5); RO (5); ES (3); US (21); CO (5); TU (11); UA (10); AU (4); CA (3); IT (4); ZA (6)