A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495)
- Conditions
- Advanced Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03516981
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. Study participants within groups defined by a biomarker-based classifier (gene expression profile \[GEP\] and tumor mutational burden \[TMB\]) will be randomized to receive pembrolizumab in combination with quavonlimab (MK-1308), favezelimab (MK-4280), or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, favezelimab, or lenvatinib, the Objective Response Rate (ORR) will be 1) greater than 5% among participants with low GEP and low TMB, 2) greater than 20% among participants with low GEP and high TMB, 3) greater than 20% among participants with high GEP and low TMB, and 4) greater than 45% among participants with high GEP and high TMB.
- Detailed Description
After Amendment 5, participants can receive 800 mg of favezelimab every 3 weeks (Q3W)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 318
- Has a histologically- or cytologically-confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC] v 8) NSCLC and has not had prior systemic therapy for advanced disease
- Has confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), c-ros oncogene 1- (ROS1-), or B isoform of rapidly accelerated fibrosarcoma- (B-Raf-) directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR mutations, B-Raf mutations, ALK gene rearrangements, and ROS1 gene rearrangements)
- Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
- Male participants must agree to use contraception during the treatment period and for ≥120 days, after the last dose of study treatment and refrain from donating sperm during this period. Male participants with pregnant partners must agree to use a condom
- Female participants eligible to participate if not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to follow contraceptive guidance during the treatment period and for ≥120 days after the last dose of study treatment
- Provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Has adequate organ function
- Has significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability, significant cardiovascular impairment, or a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram
- Prolongation of QTc interval to >480 milliseconds (ms)
- Has symptomatic ascites or pleural effusion
- Has had an allogenic tissue/solid organ transplant
- WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
- Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy, or has had major surgery within 3 weeks prior to first dose of study intervention
- Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula, gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
- Radiographic evidence of major blood vessel invasion/infiltration
- Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
- Has received prior systemic chemotherapy treatment for metastatic/recurrent NSCLC
- Has current NSCLC disease that can be treated with curative intent with surgical resection, localized radiotherapy, or chemoradiation
- Is expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor
- Has received previous treatment with another agent targeting the Lymphocyte-activation gene 3 (LAG-3) receptor
- Has received previous treatment with another agent targeting vascular endothelial growth factor (VEGF) or the VEGF receptor
- Has received prior anticancer therapy including investigational agents within 4 weeks prior to randomization
- Has received prior radiotherapy within 2 weeks of start of study treatment or received lung radiation therapy of >30 Gy within 6 months prior to the first dose of study intervention
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study treatment
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, favezelimab, or lenvatinib and/or any of its excipients
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
- Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days (females and males) after the last dose of study treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GEP low TMB low: Pembrolizumab + Quavonlimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the Recommended Phase 2 Dose (\[RP2D\], dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP low TMB low: Pembrolizumab + Favezelimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP low TMB low: Pembrolizumab + Favezelimab Favezelimab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP low TMB hi: Pembrolizumab + Favezelimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB low: Pembrolizumab + Favezelimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB low: Pembrolizumab + Favezelimab Favezelimab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB low: Pembrolizumab + Lenvatinib Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP hi TMB hi: Pembrolizumab + Quavonlimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB hi: Pembrolizumab + Favezelimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP low TMB low: Pembrolizumab + Lenvatinib Lenvatinib Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP low TMB hi: Pembrolizumab + Quavonlimab Quavonlimab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP low TMB hi: Pembrolizumab + Lenvatinib Lenvatinib Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP hi TMB low: Pembrolizumab + Lenvatinib Lenvatinib Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP hi TMB hi: Pembrolizumab + Lenvatinib Lenvatinib Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP low TMB low: Pembrolizumab + Lenvatinib Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP low TMB hi: Pembrolizumab + Quavonlimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP low TMB hi: Pembrolizumab + Favezelimab Favezelimab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP low TMB hi: Pembrolizumab + Lenvatinib Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP hi TMB low: Pembrolizumab + Quavonlimab Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB hi: Pembrolizumab + Favezelimab Favezelimab Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB hi: Pembrolizumab + Lenvatinib Pembrolizumab Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity. GEP low TMB low: Pembrolizumab + Quavonlimab Quavonlimab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the Recommended Phase 2 Dose (\[RP2D\], dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB low: Pembrolizumab + Quavonlimab Quavonlimab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). GEP hi TMB hi: Pembrolizumab + Quavonlimab Quavonlimab Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) Up to ~2 years ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by local site.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to ~2 years OS is defined as the time from randomization to death due to any cause.
Progression Free Survival (PFS) per RECIST 1.1 Up to ~2 years PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by local site.
Number of Participants Experiencing Adverse Events (AEs) Up to ~2 years An AE is any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants in each treatment arm experiencing an AE will be reported.
Number of Participants Discontinuing Study Drug Due to AEs Up to ~2 years An AE is any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants in each treatment arm that discontinued study drug due to an AE will be reported.
Trial Locations
- Locations (81)
Dolnoslaskie Centrum Onkologii. ( Site 0993)
🇵🇱Wroclaw, Dolnoslaskie, Poland
Jewish General Hospital ( Site 0307)
🇨🇦Montreal, Quebec, Canada
University of California Davis Comprehensive Cancer Center ( Site 0137)
🇺🇸Sacramento, California, United States
Seoul National University Hospital ( Site 0800)
🇰🇷Seoul, Korea, Republic of
Fondazione Policlinico Universitario A. Gemelli ( Site 0703)
🇮🇹Roma, Italy
University of Wisconsin- Madison Carbone Cancer Center ( Site 0130)
🇺🇸Madison, Wisconsin, United States
Gallipoli Medical Research Foundation ( Site 0202)
🇦🇺Brisbane, Queensland, Australia
UCLA Hematology/Oncology -Santa Monica ( Site 0108)
🇺🇸Santa Monica, California, United States
The Ottawa Hospital ( Site 0306)
🇨🇦Ottawa, Ontario, Canada
Weill Cornell Medical College ( Site 0138)
🇺🇸New York, New York, United States
Mayo Clinic Rochester - St. Mary's Hospital ( Site 0117)
🇺🇸Rochester, Minnesota, United States
Cambridge University Hospitals NHS Trust ( Site 1306)
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Memorial Sloan Kettering Cancer Center ( Site 0113)
🇺🇸New York, New York, United States
Hospital General Universitari Vall d Hebron ( Site 1100)
🇪🇸Barcelona, Spain
Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site
🇷🇺Omsk, Omskaya Oblast, Russian Federation
Univ. Pretoria and Steve Biko Academic Hospitals ( Site 2315)
🇿🇦Pretoria, Gauteng, South Africa
Severance Hospital Yonsei University Health System ( Site 0802)
🇰🇷Seoul, Korea, Republic of
National Cancer Center Hospital ( Site 2001)
🇯🇵Tokyo, Japan
The Loginov Moscow Clinical Scientific Center ( Site 1008)
🇷🇺Moscow, Moskva, Russian Federation
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0702)
🇮🇹Meldola, Emilia-Romagna, Italy
Kantonsspital St. Gallen ( Site 2102)
🇨🇭St. Gallen, Aargau, Switzerland
Hospital Universitario Ramon y Cajal ( Site 1101)
🇪🇸Madrid, Spain
The Cancer Institute Hospital of JFCR ( Site 2000)
🇯🇵Tokyo, Japan
CIUSSS du Saguenay-Lac-St-Jean ( Site 0305)
🇨🇦Chicoutimi, Quebec, Canada
CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0310)
🇨🇦Montreal, Quebec, Canada
University College London Hospital NHS Foundation Trust ( Site 1308)
🇬🇧London, London, City Of, United Kingdom
N.N. Blokhin NMRCO ( Site 1000)
🇷🇺Moscow, Moskva, Russian Federation
Azienda Ospedaliera Papardo ( Site 0706)
🇮🇹Messina, Italy
St James Hospital ( Site 2200)
🇮🇪Dublin, Ireland
Kantonsspital Graubuenden ( Site 2103)
🇨🇭Chur, Grisons, Switzerland
MED-POLONIA Sp. z o.o. ( Site 0907)
🇵🇱Poznan, Wielkopolskie, Poland
Seconda Universita degli Studi di Napoli ( Site 0704)
🇮🇹Napoli, Italy
Taipei Veterans General Hospital ( Site 1204)
🇨🇳Taipei, Taiwan
Sandton Oncology Medical Group PTY LTD ( Site 2316)
🇿🇦Sandton, Gauteng, South Africa
Seoul National University Bundang Hospital ( Site 0803)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Asan Medical Center ( Site 0801)
🇰🇷Songpa-gu, Seoul, Korea, Republic of
MPOC ( Site 2310)
🇿🇦Groenkloof Pretoria, Gauteng, South Africa
National Cheng Kung University Hospital ( Site 1202)
🇨🇳Tainan, Taiwan
Vaal Triangle Oncology Centre ( Site 2314)
🇿🇦Vereeniging, Gauteng, South Africa
Hospital Universitario 12 de Octubre ( Site 1102)
🇪🇸Madrid, Spain
Derriford Hospital ( Site 1301)
🇬🇧Plymouth, United Kingdom
Arizona Oncology Associates, PC- HAL ( Site 8001)
🇺🇸Tempe, Arizona, United States
University of Pennsylvania ( Site 0132)
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Cancer Center/Hillman Cancer Center ( Site 0104)
🇺🇸Pittsburgh, Pennsylvania, United States
Sunnybrook Health Science Centre ( Site 0304)
🇨🇦Toronto, Ontario, Canada
Princess Margaret Cancer Centre ( Site 0309)
🇨🇦Toronto, Ontario, Canada
Fiona Stanley Hospital ( Site 0201)
🇦🇺Murdoch, Western Australia, Australia
National Cancer Centre Singapore ( Site 1900)
🇸🇬Singapore, Central Singapore, Singapore
Texas Oncology-Memorial City ( Site 8006)
🇺🇸Houston, Texas, United States
Umhlanga Oncolgy Center ( Site 2311)
🇿🇦Umhlanga, Kwazulu-Natal, South Africa
Universitaetsspital Basel ( Site 2104)
🇨🇭Basel, Basel-Stadt, Switzerland
AULSS21 Regione Veneto Ospedale Mater Salutis - Legnago ( Site 0701)
🇮🇹Legnago, Verona, Italy
University of California San Francisco ( Site 0111)
🇺🇸San Francisco, California, United States
Oncology Hematology Care ( Site 8005)
🇺🇸Cincinnati, Ohio, United States
Azienda Ospedaliera Universitaria Senese ( Site 0705)
🇮🇹Siena, Italy
Samsung Medical Center ( Site 0805)
🇰🇷Seoul, Korea, Republic of
SBHI Leningrad Regional Clinical Hospital ( Site 1001)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1005)
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0112)
🇺🇸Hackensack, New Jersey, United States
Yale University School of Medicine ( Site 0100)
🇺🇸New Haven, Connecticut, United States
Mayo Clinic Florida ( Site 0115)
🇺🇸Jacksonville, Florida, United States
Texas Oncology-Tyler ( Site 8003)
🇺🇸Tyler, Texas, United States
University of Maryland ( Site 0136)
🇺🇸Baltimore, Maryland, United States
Emily Couric Clinical Cancer Center ( Site 0134)
🇺🇸Charlottesville, Virginia, United States
Northwest Cancer Specialists, P.C. ( Site 8000)
🇺🇸Vancouver, Washington, United States
Blacktown Hospital Western Sydney Local Health District ( Site 0200)
🇦🇺Blacktown, New South Wales, Australia
AOU San Luigi Gonzaga di Orbassano ( Site 0707)
🇮🇹Orbassano, Torino, Italy
Istituto Clinico Humanitas Research Hospital ( Site 0700)
🇮🇹Rozzano, Lombardia, Italy
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
🇵🇱Warszawa, Mazowieckie, Poland
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1003)
🇷🇺Ufa, Baskortostan, Respublika, Russian Federation
St Petersburg City Clinical Oncology Dispensary ( Site 1002)
🇷🇺St. Petersburg, Sankt-Peterburg, Russian Federation
Wits Clinical Research ( Site 2313)
🇿🇦Parktown-Johannesburg, Gauteng, South Africa
Cape Town Oncology Trials Pty Ltd ( Site 2312)
🇿🇦Kraaifontein, Western Cape, South Africa
Universitaetsspital Zuerich ( Site 2100)
🇨🇭Zuerich, Zurich, Switzerland
National Taiwan University Hospital ( Site 1200)
🇨🇳Taipei, Taiwan
Kaohsiung Chang Gung Memorial Hospital ( Site 1203)
🇨🇳Kaohsiung, Taiwan
Hopitaux Universitaires de Geneve HUG ( Site 2106)
🇨🇭Geneva, Geneve, Switzerland
Mid Western Cancer Centre ( Site 2201)
🇮🇪Limerick, Ireland
National University Hospital ( Site 1901)
🇸🇬Singapore, South West, Singapore
Queen Mary Hospital ( Site 1800)
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital ( Site 1801)
🇭🇰Hong Kong, Hong Kong