Study to Determine the Safety, Tolerability, Pharmacokinetics and Recommended Phase 2 Dose (RP2D) of Livmoniplimab (ABBV-151) as a Single Agent and in Combination With Budigalimab (ABBV-181) in Participants With Locally Advanced or Metastatic Solid Tumors
- Conditions
- Advanced Solid Tumors Cancer
- Interventions
- Registration Number
- NCT03821935
- Lead Sponsor
- AbbVie
- Brief Summary
The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab (ABBV-181) as well as to assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of livmoniplimab alone and in combination with budigalimab. The study will consist of 2 parts: dose escalation and dose expansion.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 364
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For Dose Escalation only: Participants with an advanced solid tumor who are considered refractory to or intolerant of all existing therapy(ies) known to provide a clinical benefit for their condition. Additionally, participants who have been offered standard therapies and refused, or who are considered ineligible for standard therapies, may be eligible for this study on a case-by-case basis, after discussion with and agreement from the sponsor. Participants with pancreatic adenocarcinoma, urothelial cancer (UC), hepatocellular carcinoma (HCC), or head and neck squamous cell carcinoma (HNSCC) who are being considered for the dose escalation cohorts must also meet the histology specific eligibility criteria described below for dose expansion.
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For Dose Expansion only participants must meet criteria specific to the type of cancer:
- Pancreatic adenocarcinoma and have disease progression during or after 1 systemic therapy (gemcitabine monotherapy or in combination with other agents, FOLFIRINOX [or another regimen including both 5-fluorouracil and oxaliplatin], capecitabine monotherapy or in combination with other agents) administered in the adjuvant, locally advanced, or metastatic setting. If the therapy was used in an adjuvant setting, disease progression must have occurred within 6 months of completing adjuvant therapy.
- UC of the bladder and urinary tract and must have progressed following treatment with:
- Cohort 4: A platinum-based regimen (administered in any line of therapy) and a programmed death 1/programmed death ligand 1 (PD1/PDL1) antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
- Cohort 11: One or more prior line of therapy in the locally advanced or metastatic setting. Participant must have experienced radiographic progression or relapse during or after a CPI (anti-PD1 or anti-PD-L1) for locally advanced or metastatic disease.
- HCC and must have disease progression during or after 1 prior line of systemic therapy.
- HNSCC (arising from the oral cavity, oropharynx, hypopharynx, or larynx) and must have progressed following treatment with platinum-based regimen (administered in any line of therapy) and a PD1/PDL1 antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
- Microsatellite stable colorectal cancer (MSS-CRC) [unselected] participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma (as determined by polymerase chain reaction (PCR)/Next-Generation sequencing (NGS) or immunohistochemistry (IHC), respectively) who have received 1-2 prior chemotherapy regimens.
- Non-small cell lung cancer (NSCLC) relapsed/refractory (R/R): Participants with histologically or cytologically confirmed advanced or metastatic NSCLC who have received 1 prior line of chemotherapy and 1 prior anti-PD-(L)1 antibody, administered either concurrently or sequentially in the metastatic setting.
- MSS-CRC (CMS4 enriched): Participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma who have received prior fluorouracil-based combination chemotherapy regimens including oxaliplatin and irinotecan (with or without VEGF and/or EGFR targeted agents) and with a CMS4 subtype as determined by NGS of tumor biopsies. Archival tissue must be submitted for assessment of CMS4 subtype status during prescreening. Participants must have progressed on or refused available standard of care therapies. Additionally, participant who are considered not appropriate or ineligible for available standard of care therapies per investigator assessment will be eligible for this study.
- Ovarian granulosa (OG) cell tumor: Participants with histologically confirmed advanced nonresectable or metastatic adult granulosa cell tumor of the ovary that is not amenable to curative intent surgery or radiation. Additionally, there is documentation of radiological evidence of relapse after at least 1 line of systemic chemotherapy.
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Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
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Participant has adequate bone marrow, renal, hepatic, and coagulation function.
-
Must have a viral status consistent with the requirements described in the protocol specific to type of cancer and stage of study (Dose Escalation or Dose Expansion).
-
For Dose Expansion only:
- Participants with HCC, pancreatic adenocarcinoma, or MSS-CRC having prior exposure to a prior PD-1/PD-L1 antagonist in any line of therapy.
- Participants (except for participants with urothelial cancer or HNSCC) who have had prior exposure to immunotherapies as listed in the protocol.
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Has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives or 28 days (whichever is shorter), prior to the first dose of the study drug.
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Participant has unresolved AEs > Grade 1 from prior anticancer therapy except for alopecia.
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Has a history of primary immunodeficiency, bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
-
Has a known uncontrolled metastases to the central nervous system (with certain exceptions).
-
Current or prior use of immunosuppressive medication within 14 days prior to the first dose of the study drug.
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Has clinically significant uncontrolled condition(s).
-
History of inflammatory bowel disease, interstitial lung disease or pneumonitis, myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms (DRESS).
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Live vaccine administration <= 28 days prior to the first dose of study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation: Cohort 1 Livmoniplimab Livmoniplimab Various doses of Livmoniplimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D). Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab Budigalimab Various doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D). Dose Expansion: Cohort 3 Livmoniplimab + Budigalimab Budigalimab Participants with programmed cell death protein 1 (PD-1)-naïve pancreatic adenocarcinoma will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 4 Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 4 Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 5 Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-naïve hepatocellular carcinoma (HCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 6 Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-ref head and neck squamous cell carcinoma (HNSCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 7 Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-naïve microsatellite stable colorectal cancer (MSS-CRC) \[unselected\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 7 Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-naïve microsatellite stable colorectal cancer (MSS-CRC) \[unselected\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 12B Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 12B Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 8 Livmoniplimab + Budigalimab Budigalimab Participants with non-small cell lung cancer (NSCLC) \[programmed death ligand 1 (PDL1) relapsed/refractory (R/R)\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 10A Livmoniplimab + Budigalimab Budigalimab Participants with microsatellite stable colorectal cancer (MSS-CRC) \[consensus molecular subtype 4 (CMS4) enriched\] will receive livmoniplimab at the dose B Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 11A Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 11B Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 11C Budigalimab Budigalimab Participants with PD-1-ref urothelial cancer will receive budigalimab Dose B administered Q3W. Dose Expansion: Cohort 12A Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W. Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab Livmoniplimab Various doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D). Dose Expansion: Cohort 3 Livmoniplimab + Budigalimab Livmoniplimab Participants with programmed cell death protein 1 (PD-1)-naïve pancreatic adenocarcinoma will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 8 Livmoniplimab + Budigalimab Livmoniplimab Participants with non-small cell lung cancer (NSCLC) \[programmed death ligand 1 (PDL1) relapsed/refractory (R/R)\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 5 Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-naïve hepatocellular carcinoma (HCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 6 Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-ref head and neck squamous cell carcinoma (HNSCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W. Dose Expansion: Cohort 10A Livmoniplimab + Budigalimab Livmoniplimab Participants with microsatellite stable colorectal cancer (MSS-CRC) \[consensus molecular subtype 4 (CMS4) enriched\] will receive livmoniplimab at the dose B Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 10B Livmoniplimab + Budigalimab Livmoniplimab Participants with MSS-CRC (CMS4 enriched) will receive livmoniplimab at the dose C Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 11A Livmoniplimab + Budigalimab Livmoniplimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 11B Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 12A Livmoniplimab + Budigalimab Budigalimab Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W. Dose Expansion: Cohort 10B Livmoniplimab + Budigalimab Budigalimab Participants with MSS-CRC (CMS4 enriched) will receive livmoniplimab at the dose C Q3W plus budigalimab Dose B administered Q3W.
- Primary Outcome Measures
Name Time Method Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy Up to 28 days after the first dose of Livmoniplimab monotherapy The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation portion of the study.
Dose Escalation: RP2D Livmoniplimab + Budigalimab Combination Therapy Up to 28 days after the first dose of Livmoniplimab and Budigalimab combination therapy The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.
Dose Expansion: Objective Response Rate (ORR) Up to approximately 6 months after the first dose date of last participant in Dose Expansion ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Secondary Outcome Measures
Name Time Method Dose Expansion: Duration of Response (DOR) Up to approximately 6 months after the first dose date of last participant in Dose Expansion The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
Dose Expansion: Progression-free Survival (PFS) Up to approximately 6 months after the first dose date of last participant in Dose Expansion Progression-free survival is defined as the time from the participant's first dose of study treatment (livmoniplimab or budigalimab) to the first date of either disease progression or death, whichever occurs first.
Maximum Observed Serum Concentration (Cmax) of Livmoniplimab Up to approximately 70 days after initial dose of study drug Maximum Serum Concentration (Cmax) of livmoniplimab.
Change in Electrocardiogram (ECG) Up to approximately 6 months after the first dose date of last participant 12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.
Incidence of Anti-drug Antibody (ADA) Up to approximately 6 months after the first dose date of last participant The number of participants with anti-drug antibodies.
Dose Expansion Cohorts 10 to 12: Overall Survival (OS) Up to approximately 6 months after the first dose date of last participant in Cohorts 10 to 12 OS is defined as time from first study treatment to death due to any cause.
Time to Maximum Observed Serum Concentration (Tmax) of Livmoniplimab Up to approximately 70 days after initial dose of study drug Time to maximum serum concentration (Tmax) of livmoniplimab.
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Livmoniplimab Up to approximately 70 days after initial dose of study drug Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of livmoniplimab.
Terminal-phase Elimination Rate Constant (β) of Livmoniplimab Up to approximately 70 days after initial dose of study drug Apparent terminal phase elimination rate constant (β or Beta) of livmoniplimab.
Terminal Phase Elimination Half-life (t1/2) of Livmoniplimab Up to approximately 70 days after initial dose of study drug Terminal phase elimination half-life (t1/2) of livmoniplimab.
Maximum Observed Serum Concentration (Cmax) of Budigalimab Up to approximately 70 days after initial dose of study drug Maximum Serum Concentration (Cmax) of budigalimab.
Time to Maximum Observed Serum Concentration (Tmax) of Budigalimab Up to approximately 70 days after initial dose of study drug Time to maximum serum concentration (Tmax) of budigalimab.
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Budigalimab Up to approximately 70 days after initial dose of study drug Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of budigalimab.
Terminal-phase Elimination Rate Constant (β) of Budigalimab Up to approximately 70 days after initial dose of study drug Apparent terminal phase elimination rate constant (β or Beta) of budigalimab.
Terminal Phase Elimination Half-life (t1/2) of Budigalimab Up to approximately 70 days after initial dose of study drug Terminal phase elimination half-life (t1/2) of budigalimab.
Number of Participants With Adverse Events (AEs) Up to approximately 9 months after the first dose date of last participant An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Change in Vital Signs Up to approximately 6 months after the first dose date of last participant Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.
Change in Laboratory Parameters Up to approximately 6 months after the first dose date of last participant Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.
Trial Locations
- Locations (64)
Rabin Medical Center /ID# 258479
🇮🇱Petah Tikva, Israel
Taipei Veterans General Hosp /ID# 257635
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital /ID# 265551
🇨🇳Taoyuan City, Taiwan
NEXT Oncology /ID# 208930
🇺🇸San Antonio, Texas, United States
Highlands Oncology Group, PA /ID# 218942
🇺🇸Springdale, Arkansas, United States
City of Hope National Medical Center /ID# 265620
🇺🇸Duarte, California, United States
City of Hope Orange County Lennar Foundation Cancer Center /ID# 270785
🇺🇸Irvine, California, United States
Yale University School of Medicine /ID# 208356
🇺🇸New Haven, Connecticut, United States
AdventHealth Celebration /ID# 224860
🇺🇸Celebration, Florida, United States
Duplicate_AdventHealth Cancer Institute - Orlando /ID# 226953
🇺🇸Orlando, Florida, United States
Indiana Univ School Medicine /ID# 208384
🇺🇸Indianapolis, Indiana, United States
Community Health Network, Inc. /ID# 257032
🇺🇸Indianapolis, Indiana, United States
Univ Michigan Med Ctr /ID# 221129
🇺🇸Ann Arbor, Michigan, United States
Washington University-School of Medicine /ID# 259684
🇺🇸Saint Louis, Missouri, United States
Intermountain Health West End Clinic Gynecologic Oncology /ID# 266171
🇺🇸Billings, Montana, United States
NYU Langone Medical Center /ID# 209822
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai /ID# 264653
🇺🇸New York, New York, United States
Carolina BioOncology Institute /ID# 208358
🇺🇸Huntersville, North Carolina, United States
The Ohio State University - The James /ID# 217611
🇺🇸Columbus, Ohio, United States
Ou Health - Stephenson Cancer Center /ID# 268826
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute (SMO/Network/Consortium) /ID# 264900
🇺🇸Nashville, Tennessee, United States
Renovatio clinical /ID# 265109
🇺🇸El Paso, Texas, United States
Renovatio Clinical /ID# 265054
🇺🇸The Woodlands, Texas, United States
University of Washington Medical Center /ID# 268854
🇺🇸Seattle, Washington, United States
Chris O'Brien Lifehouse /ID# 213236
🇦🇺Camperdown, New South Wales, Australia
Icon Cancer Centre /ID# 224961
🇦🇺South Brisbane, Queensland, Australia
Cliniques Universitaires UCL Saint-Luc /ID# 218466
🇧🇪Bruxelles, Bruxelles-Capitale, Belgium
University Health Network_Princess Margaret Cancer Centre /ID# 209423
🇨🇦Toronto, Ontario, Canada
CHU Toulouse - Hopital Purpan /ID# 218667
🇫🇷TOULOUSE Cedex 9, Haute-Garonne, France
Centre Leon Berard /ID# 218515
🇫🇷Lyon CEDEX 08, Rhone, France
Institut Gustave Roussy /ID# 218668
🇫🇷Villejuif Cedex, Val-de-Marne, France
Centre Jean Perrin /ID# 218669
🇫🇷Clermont Ferrand, France
Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung /ID# 269587
🇩🇪Essen, Nordrhein-Westfalen, Germany
Rambam Health Care Campus /ID# 222198
🇮🇱Haifa, H_efa, Israel
The Chaim Sheba Medical Center /ID# 209037
🇮🇱Ramat Gan, Tel-Aviv, Israel
Tel Aviv Sourasky Medical Center /ID# 222199
🇮🇱Tel Aviv, Tel-Aviv, Israel
Hadassah Medical Center-Hebrew University /ID# 257918
🇮🇱Jerusalem, Israel
Istituto Europeo Di Oncologia /Id# 266053
🇮🇹Milan, Milano, Italy
National Cancer Center Hospital East /ID# 224808
🇯🇵Kashiwa-shi, Chiba, Japan
Hyogo Cancer Center /ID# 272553
🇯🇵Akashi-shi, Hyogo, Japan
National Cancer Center Hospital /ID# 209421
🇯🇵Chuo-ku, Tokyo, Japan
Gachon University Gil Medical Center /ID# 257572
🇰🇷Incheon, Gyeonggido, Korea, Republic of
Chonnam National University Hwasun Hospital /ID# 257573
🇰🇷Hwasun-gun, Jeonranamdo, Korea, Republic of
Korea University Anam Hospital /ID# 257574
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital /ID# 218513
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center /ID# 266799
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Samsung Medical Center /ID# 265865
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 218512
🇰🇷Seoul, Korea, Republic of
Instytut Centrum Zdrowia Matki Polki /ID# 266324
🇵🇱Lodz, Lodzkie, Poland
Jagiellonskie Centrum Innowacji Sp. z o.o. /ID# 266194
🇵🇱Krakow, Malopolskie, Poland
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 266147
🇵🇱Warszawa, Mazowieckie, Poland
Pan American Center for Oncology Trials, LLC /ID# 217475
🇵🇷Rio Piedras, Puerto Rico
Clinica Universidad de Navarra - Pamplona /ID# 266632
🇪🇸Pamplona, Navarra, Spain
Hospital Universitari Vall d'Hebron /ID# 265290
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona /ID# 221106
🇪🇸Barcelona, Spain
Clinica Universidad de Navarra - Madrid /ID# 265299
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal /ID# 265298
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz /ID# 220928
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro /ID# 265294
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia /ID# 221107
🇪🇸Valencia, Spain
Kaohsiung Chang Gung Memorial Hospital /ID# 265560
🇨🇳Kaohsiung City, Kaohsiung, Taiwan
National Taiwan University Hospital /ID# 218490
🇨🇳Taipei City, Taipei, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 257634
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital /ID# 218492
🇨🇳Taichung, Taiwan