Sponsor: Merck Sharp & Dohme LLC (industry)
Phase: 3
Start date: April 14, 2024
Planned enrollment: 1200
Sacituzumab tirumotecan (sac-TMT), also known as SKB264 or MK-2870, is an investigational antibody-drug conjugate (ADC) targeting TROP2, a cell surface glycoprotein overexpressed in various cancers. (prnewswire.com)
Sac-TMT comprises a monoclonal antibody directed against TROP2 linked to a topoisomerase I inhibitor payload. This design facilitates targeted delivery of the cytotoxic agent to TROP2-expressing tumor cells, aiming to enhance antitumor efficacy while minimizing systemic toxicity. (prnewswire.com)
Endometrial and Ovarian Cancers
In the phase 2 KL264-01 trial (NCT04152499), sac-TMT monotherapy was evaluated in patients with previously treated advanced endometrial and ovarian cancers. Preliminary results presented at the 2024 ESMO Congress showed:
Median Duration of Response (DOR): 5.7 months (range, 3.8 to 7.4+)
Ovarian Cancer Cohort (n = 40):
Triple-Negative Breast Cancer (TNBC)
The phase 3 OptiTROP-Breast01 study (NCT05347134) compared sac-TMT to physician's choice of chemotherapy in patients with previously treated locally recurrent or metastatic TNBC. Results indicated:
Median Overall Survival (OS): Not reached (95% CI, 11.2 to NE)
Chemotherapy Arm (n = 133):
Sac-TMT demonstrated a statistically significant improvement in PFS and OS compared to chemotherapy. (ascopubs.org)
In the KL264-01 trial, treatment-related adverse events (TRAEs) occurred in all patients:
Common TRAEs: Anemia (88.6%), decreased white blood cell count (81.8%), decreased neutrophil count (65.9%)
Ovarian Cancer Cohort:
No TRAEs led to death, and there were no reports of drug-related interstitial lung disease or pneumonitis. (onclive.com)
In the OptiTROP-Breast01 study, common grade ≥3 TRAEs in the sac-TMT arm included:
Last updated: Apr 2025
Last updated: Aug 2025
Goal: The goal of the trial is to evaluate whether sacituzumab tirumotecan, either as a single agent or in combination with pembrolizumab, provides superior progression-free survival compared to standard chemotherapy of physician’s choice in HR+/HER2- unresectable locally advanced or metastatic breast cancer.
Patients: The trial is enrolling adults with unresectable locally advanced or metastatic, centrally-confirmed HR+/HER2- breast cancer who have progressed on at least one prior line of endocrine therapy (which must include a CDK4/6 inhibitor) and are candidates for chemotherapy. Patients must have ECOG 0-1 and adequate organ function. Individuals with certain comorbidities or a history of active autoimmune disease or prior chemotherapy in the metastatic setting are excluded.
Design: The study is an open-label, randomized, phase 3 trial with three arms. Patients are randomized to receive sacituzumab tirumotecan, sacituzumab tirumotecan plus pembrolizumab, or the physician’s choice of standard chemotherapy.
Treatments: Sacituzumab tirumotecan is an investigational antibody-drug conjugate targeting TROP2 and delivering a belotecan-derived topoisomerase I inhibitor via a pH-sensitive linker, enabling robust bystander killing. Previous phase III trials in other cancers, such as triple-negative breast cancer, have shown significant improvements in progression-free and overall survival versus chemotherapy, with expected toxicities mainly being myelosuppression. Pembrolizumab is an anti-PD-1 checkpoint inhibitor, and the combination aims to synergize cytotoxic and immune-mediated effects. The comparator arm consists of standard single-agent chemotherapies including paclitaxel (weekly or every 4 weeks), nab-paclitaxel, capecitabine, or liposomal doxorubicin, which are all commonly used in this patient population.
Outcomes: The primary outcome is progression-free survival by blinded central review per RECIST 1.1. Key secondary outcomes include overall survival, progression-free survival comparing combination versus monotherapy, objective response rate, duration of response, adverse event profile, treatment discontinuation due to adverse events, and patient-reported outcomes including quality of life, physical and emotional functioning, fatigue, and diarrhea as measured by the EORTC QLQ-C30.
Burden on patient: The trial is expected to carry a moderate burden for patients, comparable to other phase 3 studies in this setting. As treatments are mostly intravenous with visits every 2 or 6 weeks and oral quality-of-life questionnaires, the logistics are similar to current standards of care. No extra mandatory biopsies or high-frequency blood sampling are specified, so the overall visit and testing schedule should not exceed what is typical for metastatic breast cancer trials utilizing IV chemotherapy or antibody-drug conjugates.
Inclusion Criteria:
* Has unresectable locally advanced or metastatic centrally-confirmed hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer
* Has radiographic disease progression on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor
* Is a chemotherapy candidate
* Has an eastern cooperative oncology group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization
* Has adequate organ function
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
* Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion Criteria:
* Has breast cancer amenable to treatment with curative intent
* Has experienced an early recurrence (\<6 months after completing adjuvant/neoadjuvant chemotherapy) and therefore is eligible to receive second-line (2L) treatment
* Has symptomatic advanced/metastatic visceral spread at risk of rapidly evolving into life-threatening complications
* Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
* Active autoimmune disease that has required systemic treatment in the past 2 years
* History of (noninfectious) pneumonitis/interstitial lung disease that requires steroids, or has current pneumonitis/interstitial lung disease
* Has an active infection requiring systemic therapy
Ciudad Autónoma de Buenos Aires, Caba, 1426ANZ, Argentina
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Rosario, Santa Fe, S2000DEJ, Argentina
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La Rioja, F5300COE, Argentina
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Macquarie University, New South Wales, 2109, Australia
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Westmead, New South Wales, 2145, Australia
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Frankston, Victoria, 3199, Australia
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Brussels, Bruxelles-Capitale, Region De, 1200, Belgium
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Teresina, Piaui, 64049-200, Brazil
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Porto Alegre, Rio Grande Do Sul, 90035-001, Brazil
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Santa Cruz do Sul, Rio Grande Do Sul, 96830-180, Brazil
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Porto Alegre, Rio Grande Do Sul, 90110-270, Brazil
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Taubaté, Sao Paulo, 12030-200, Brazil
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Santiago., Region M. De Santiago, 7500994, Chile
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Santiago, Region M. De Santiago, 8420383, Chile
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Santiago, Region M. De Santiago, 8330024, Chile
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Santiago, Region M. De Santiago, 7500921, Chile
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San José, San Jose, 10103, Costa Rica
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Santa Ana, San Jose, 10903, Costa Rica
No email / No phone
Status: Active, not recruiting
San Jose, 10108, Costa Rica
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Ceske Budejovice, Jihocesky Kraj, 370 01, Czechia
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Olomouc, Olomoucky Kraj, 779 00, Czechia
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Praha, Praha 5, 150 06, Czechia
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Praha 10, 100 34, Czechia
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Copenhagen, Hovedstaden, 2100, Denmark
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Hillerod, Hovedstaden, 3400, Denmark
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Naestved, Sjaelland, 4700, Denmark
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Odense C, Syddanmark, 5000, Denmark
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Caen, Calvados, 14076, France
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Montpellier, Languedoc-Roussillon, 34070, France
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Nantes, Loire-Atlantique, 44277, France
No email / 33228272088
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Paris, Orne, 75013, France
No email / 33142160097
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Lyon, Rhone-Alpes, 69008, France
No email / 33437538725
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Poitiers, Vienne, 86021, France
No email / 33549444548
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Paris, 75248, France
No email / +33144324675
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Athens, Attiki, 115 26, Greece
No email / +302106972433
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Marousi, Attiki, 151 23, Greece
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Athens, Attiki, 115 28, Greece
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Thessaloniki, Kentriki Makedonia, 552 36, Greece
No email / +302310390671
Status: Recruiting
Larissa, Thessalia, 411 10, Greece
No email / +302413502785
Status: Recruiting
Thessaloniki, 57001, Greece
No email / +302313252011
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Shatin, Hong Kong
No email / +852 3505 2211
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Hksar, Hong Kong
No email / QMH- +852 2255 3838
Status: Recruiting
Szeged, Csongrad, 6720, Hungary
No email / 3662545404
Status: Recruiting
Kaposvár, Somogy, 7400, Hungary
No email / 36304111268
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Zalaegerszeg, Zala, 8900, Hungary
No email / 36304199969
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Budapest, 1145, Hungary
No email / +36209674709
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Debrecen, 4032, Hungary
No email / +3652255585
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New Delhi, Delhi, 110085, India
No email / 8005328138
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New Delhi, Delhi, 110029, India
No email / 504326588500
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Mumbai, Maharashtra, 400012, India
No email / 9967111418
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Mumbai, Maharashtra, 400053, India
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Dublin, D07 R2WY, Ireland
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Cork, T12 DV56, Ireland
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Haifa, 3109601, Israel
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Petah Tikva, 4941492, Israel
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Ramat Gan, 5265601, Israel
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Meldola, Forli-Cesena, 47014, Italy
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Aviano, Friuli-Venezia Giulia, 33081, Italy
No email / +39 0434659514
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Milan, Lombardia, 20133, Italy
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Milano, Lombardia, 20141, Italy
No email / +02 57489970
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Rozzano, Milano, 20089, Italy
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Milano, 20132, Italy
No email / +390226436530
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Bologna, 40138, Italy
No email / +39 0512144548
Status: Recruiting
Genova, 16132, Italy
No email / +390105600387
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Roma, 00168, Italy
No email / +3930156318
Status: Recruiting
Nagoya, Aichi, 467-8602, Japan
No email / +81-52-858-7215
Status: Recruiting
Sapporo, Hokkaido, 060-8648, Japan
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Isehara, Kanagawa, 259-1193, Japan
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Yokohama, Kanagawa, 241-8515, Japan
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Sagamihara, Kanagawa, 252-0375, Japan
No email / +81-42-778-9965
Status: Recruiting
Kawasaki, Kanagawa, 216-8511, Japan
No email / +81-44-977-8111
Status: Recruiting
Tsu, Mie, 514-8507, Japan
No email / +81-59-231-5246
Status: Recruiting
Sendai, Miyagi, 980-8574, Japan
No email / +81-22-717-7000
Status: Recruiting
Suita, Osaka, 565-0871, Japan
No email / +81-6-6210-8290
Status: Recruiting
Hidaka, Saitama, 350-1298, Japan
No email / +81-42-984-4111
Status: Recruiting
Bunkyo, Tokyo, 113-8431, Japan
No email / +81-3-3813-3111
Status: Recruiting
Koto, Tokyo, 135-8550, Japan
No email / +81-3-3520-0111
Status: Recruiting
Shinjuku, Tokyo, 162-8655, Japan
No email / +81-3-3202-7181
Status: Recruiting
Shinjuku, Tokyo, 160-0023, Japan
No email / +81-3-3342-6111
Status: Recruiting
Shinagawa, Tokyo, 142-8666, Japan
No email / +81-3-3784-8000
Status: Recruiting
Kagoshima, 892-0833, Japan
No email / +81-99-224-1800
Status: Recruiting
Fukushima, 960-1295, Japan
No email / +81-24-547-1111
Status: Recruiting
Gifu, 501-1194, Japan
No email / +81-58-230-6000
Status: Recruiting
Hiroshima, 730-8518, Japan
No email / +81-82-221-2291
Status: Recruiting
Kumamoto, 860-8556, Japan
No email / +81-96-344-2111
Status: Recruiting
Kyoto, 606-8507, Japan
No email / +81-75-751-4389
Status: Recruiting
Okayama, 700-8558, Japan
No email / +81-86-223-7151
Status: Recruiting
Osaka, 541-8567, Japan
No email / +81-6-6945-1181
Status: Recruiting
Seoul, 03722, Korea, Republic of
No email / 82222288135
Status: Recruiting
Seoul, 03080, Korea, Republic of
No email / No phone
Status: Active, not recruiting
Seoul, 05505, Korea, Republic of
No email / +82230105397
Status: Recruiting
Seoul, 06351, Korea, Republic of
No email / 82234106833
Status: Recruiting
Johor Bahru, Johor, 81100, Malaysia
No email / +6073565155
Status: Recruiting
Kuching, Sarawak, 93586, Malaysia
No email / +6082276820
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Kuala Lumpur, 59100, Malaysia
No email / +60327814519
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Ciudad de México, Distrito Federal, 03100, Mexico
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Guadalajara, Jalisco, 44630, Mexico
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Monterrey, Nuevo Leon, 64460, Mexico
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San Pedro Garza Garcia, Nuevo Leon, 66278, Mexico
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Arnhem, Gelderland, 6815 AD, Netherlands
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Maastricht, Limburg, 6229 HX, Netherlands
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Breda, Noord-Brabant, 4800 RK, Netherlands
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Eindhoven, Noord-Brabant, 5623 EJ, Netherlands
No email / +31402396622
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Amsterdam, Noord-Holland, 1066 CX, Netherlands
No email / +31205129111
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Zwolle, Overijssel, 8025 AB, Netherlands
No email / +31886246040
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Amersfoort, Utrecht, 3813TZ, Netherlands
No email / +31338507278
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Auckland, 1023, New Zealand
No email / +6493074949
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Arequipa, Ariqipa, 15036, Peru
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Jesús María, Lima, 18, Peru
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Bydgoszcz, Kujawsko-pomorskie, 85-796, Poland
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Warszawa, Mazowieckie, 02-781, Poland
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Siedlce, Mazowieckie, 08-110, Poland
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Wieliszew, Mazowieckie, 05-135, Poland
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Rzeszow, Podkarpackie, 35-021, Poland
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Bialystok, Podlaskie, 15-027, Poland
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Gdynia, Pomorskie, 81-519, Poland
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Status: Recruiting
Gliwice, Slaskie, 44-102, Poland
No email / 1-888-577-8839
Status: Recruiting
Kielce, Swietokrzyskie, 25-734, Poland
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Koszalin, Zachodniopomorskie, 75-581, Poland
No email / 0048943488937
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Szczecin, Zachodniopomorskie, 71-730, Poland
No email / 1-888-577-8839
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Lisbon, Lisboa, 2720-276, Portugal
No email / 00351214348200
Status: Recruiting
Lisboa, 1649-035, Portugal
No email / 00351217805000
Status: Recruiting
Porto, 4200-072, Portugal
No email / 00351225084000
Status: Recruiting
San Juan, 00935, Puerto Rico
No email / 7877728300 Ext 1226
Status: Recruiting
Hato Rey, 00917, Puerto Rico
No email / 7876106292
Status: Recruiting
București, Bucuresti, 011171, Romania
No email / 0040213188930
Status: Recruiting
Florești, Cluj, 407280, Romania
No email / 0040219368
Status: Recruiting
Bucuresti, 077190, Romania
No email / 0040217948731
Status: Recruiting
Cluj, 400015, Romania
No email / 0040264598362
Status: Recruiting
Singapore, Central Singapore, 119074, Singapore
No email / +6569082222
Status: Recruiting
Singapore, North East, 574623, Singapore
No email / +6562550528
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Port Elizabeth, Eastern Cape, 6055, South Africa
No email / 041 450 6152
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Sandton, Gauteng, 2196, South Africa
No email / +27118830900
Status: Recruiting
Pretoria, Gauteng, 0084, South Africa
No email / +27123356771
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Rondebosch, Western Cape, 7700, South Africa
No email / +279443700
Status: Recruiting
Pozuelo de Alarcon, Madrid, 28223, Spain
No email / +34914521987
Status: Recruiting
Valencia, Valenciana, Comunitat, 46010, Spain
No email / +34961973583
Status: Recruiting
Cordoba, 14004, Spain
No email / +34957511464
Status: Recruiting
Barcelona, 08035, Spain
No email / +34932746000
Status: Recruiting
Madrid, 28007, Spain
No email / +34914097423
Status: Recruiting
Madrid, 28009, Spain
No email / +3491 426 93 92
Status: Recruiting
Sevilla, 41009, Spain
No email / +34955008000
Status: Recruiting
Stockholm, Stockholms Lan, 171 76, Sweden
No email / +46812370000
Status: Recruiting
Uppsala, Uppsala Lan, 75185, Sweden
No email / +46186110000
Status: Recruiting
Borås, Vastra Gotalands Lan, 501 82, Sweden
No email / 1-888-577-8839
Status: Recruiting
Basel, Basel-Stadt, 4031, Switzerland
No email / 1-888-577-8839
Status: Recruiting
Thun, Berne, 3600, Switzerland
No email / 1-888-577-8839
Status: Recruiting
Zürich, Zurich, 8008, Switzerland
No email / 1-888-577-8839
Status: Recruiting
Changhua, 50006, Taiwan
No email / No phone
Status: Completed
Tainan, 704, Taiwan
No email / 1-888-577-8839
Status: Recruiting
Kaohsiung, 83301, Taiwan
No email / 1-888-577-8839
Status: Recruiting
Taipei, 10449, Taiwan
No email / 1-888-577-8839
Status: Recruiting
Taipei, 10002, Taiwan
No email / 886-2-23123456x71673
Status: Recruiting
Taoyuan, 333, Taiwan
No email / 1-888-577-8839
Status: Recruiting
Yenimahalle, Ankara, 06200, Turkey
No email / 0090 506 366 5181
Status: Recruiting
Stanbul, Istanbul, 34214, Turkey
No email / 1-888-577-8839
Status: Recruiting
Samsun, 55200, Turkey
No email / 1-888-577-8839
Status: Recruiting
Ankara, 06800, Turkey
No email / 905426121216
Status: Recruiting
Ankara, 06520, Turkey
No email / 00905067521275
Status: Recruiting
Ankara, 06230, Turkey
No email / +905427212606
Status: Recruiting
Adana, 01140, Turkey
No email / 905056166338
Status: Recruiting
Istanbul, 34722, Turkey
No email / 1-888-577-8839
Status: Recruiting
Londonderry, Derry And Strabane, BT47 6SB, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Truro, England, TR1 3LJ, United Kingdom
No email / +441872258343
Status: Recruiting
London, London, City Of, EC1A 7BE, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
London, London, City Of, NW1 2PG, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Nottingham, NG5 1PB, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Blackpool, FY3 8NR, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Chandler, Arizona, 85224, United States
No email / 888-577-8839
Status: Recruiting
Gilbert, Arizona, 85234, United States
No email / 480-256-6444
Status: Recruiting
La Jolla, California, 92093-0698, United States
No email / 888-577-8839
Status: Recruiting
Fullerton, California, 92835, United States
No email / 714-446-5900
Status: Recruiting
Los Alamitos, California, 90720, United States
No email / 888-577-8839
Status: Recruiting
Denver, Colorado, 80206, United States
No email / 720-848-1030
Status: Recruiting
Aurora, Colorado, 80045, United States
No email / 888-577-8839
Status: Recruiting
New Haven, Connecticut, 06510, United States
No email / 888-577-8839
Status: Recruiting
Stamford, Connecticut, 06904, United States
No email / 888-577-8839
Status: Recruiting
Orlando, Florida, 32806, United States
No email / 888-577-8839
Status: Recruiting
Altamonte Springs, Florida, 32701, United States
No email / 888-577-8839
Status: Recruiting
Gainesville, Florida, 32610, United States
No email / 888-577-8839
Status: Recruiting
Thomasville, Georgia, 31792, United States
No email / 229-584-5400
Status: Recruiting
Chicago, Illinois, 60637, United States
No email / 888-577-8839
Status: Recruiting
Edgewood, Kentucky, 41017, United States
No email / 888-577-8839
Status: Recruiting
Baton Rouge, Louisiana, 70817, United States
No email / 888-577-8839
Status: Recruiting
Baltimore, Maryland, 21202, United States
No email / 888-577-8839
Status: Recruiting
Baltimore, Maryland, 21201, United States
No email / 410-328-6373
Status: Recruiting
Silver Spring, Maryland, 20910, United States
No email / 301-754-7000
Status: Recruiting
Boston, Massachusetts, 02215, United States
No email / 888-577-8839
Status: Recruiting
Saint Louis, Missouri, 63110, United States
No email / 314-454-8313
Status: Recruiting
Stony Brook, New York, 11794, United States
No email / 888-577-8839
Status: Recruiting
Nyack, New York, 10960, United States
No email / 888-577-8839
Status: Recruiting
Charlotte, North Carolina, 28204, United States
No email / 980-442-2000
Status: Recruiting
Portland, Oregon, 97225, United States
No email / 503-215-2619
Status: Recruiting
Portland, Oregon, 97213, United States
No email / 503-215-2619
Status: Recruiting
Philadelphia, Pennsylvania, 19107, United States
No email / 215-955-8874
Status: Recruiting
San Antonio, Texas, 78240, United States
No email / 212-241-0493
Status: Recruiting
Dallas, Texas, 75231, United States
No email / 214-265-2080
Status: Recruiting
Fort Worth, Texas, 76104, United States
No email / 888-577-8839
Status: Recruiting
Tyler, Texas, 75701, United States
No email / 903-595-7093
Status: Recruiting
Midlothian, Virginia, 23114, United States
No email / 888-577-8839
Status: Recruiting
Fairfax, Virginia, 22031, United States
No email / 501-650-1726
Status: Recruiting
Roanoke, Virginia, 24014, United States
No email / 540-982-0237
Status: Recruiting
Richmond, Virginia, 23219, United States
No email / 888-577-8839
Status: Recruiting
Madison, Wisconsin, 53792, United States
No email / 888-577-8839
Status: Recruiting