Study Comparing Investigational Drug HBI-8000 + Nivolumab vs. Placebo + Nivolumab in Patients With Advanced Melanoma

Phase 3

Active, not recruiting

• Conditions: Unresectable or Metastatic Melanoma; Progressive Brain Metastasis
• Interventions: Drug: HBI-8000 in combination with nivolumab; Drug: Placebo in combination with nivolumab

• Registration Number: NCT04674683
• Lead Sponsor: HUYABIO International, LLC.

Brief Summary

This is a clinical study to compare the efficacy and safety of HBI-8000 combined with nivolumab to Placebo combined with nivolumab in patients with unresectable or metastatic melanoma. A separate open-label cohort of adults with new, progressive brain metastasis or adolescents with or without new progressive brain metastasis receive HBI-8000 combined with nivolumab.

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab. Randomization of eligible patients will be stratified by PD-L1 expression (positive, ≥1% expression level versus negative, \<1% expression level) and LDH (normal versus elevated) in the main study. Adults with new, progressive brain metastasis, or adolescents with or without new progressive brain metastasis will be enrolled in a separate, non-randomized, open-label cohort to receive the combination of HBI-8000 and nivolumab.

In the main study, eligible patients will be randomized within the appropriate stratum at a 1:1 ratio to the Test arm or the Control arm. Study treatment will be initiated within 3 days of randomization.

A treatment cycle consists of 28 days. Patients will be treated with one of the following:

Test arm: HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days

Control arm: Placebo oral BIW + nivolumab IV at specific doses on specific days

The Study Treatment (HBI-8000 or Placebo) is administered approximately 30 minutes after a full meal.

The Study Treatment (HBI-8000 or Placebo) will be administered twice a week on the following days of every 28-day cycle:

* CxW1: Days 1, 4

* CxW2: Days 8, 11

* CxW3: Days 15, 18

* CxW4: Days 22, 25

Study treatment must commence within 3 days after randomization and continue up to 2 years or until disease progression (confirmed), unacceptable toxicity or patient withdrawal of consent.

In addition to Study Treatment, nivolumab is administered at specific doses on specific days as an intravenous infusion over approximately 30 minutes. Nivolumab will be administered on Day 1 of each cycle.

For non-randomized cohort for special population, eligible subjects will receive HBI-8000 30 mg oral BIW and nivolumab IV at specific doses on specific days, under the same schedule as described above. For adolescents weighing \< 40 kg, nivolumab will be dosed at specific doses every 4 weeks. Nivolumab will be administered on Day 1 of each cycle.

Study Timeline

• Study First Submitted: 2020-12-07
• Study First Submitted QC: 2020-12-14
• Study First Posted: 2020-12-19
• Study Start: 2021-08-12
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-19
• Last Update Posted: 2024-06-24
• Primary Completion: 2024-12
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1. Histopathologically confirmed diagnosis of non-uveal, Stage III (unresectable), or Stage IV (metastatic) melanoma according to AJCC staging system (8th edition).

2. Known BRAF V600 mutation status or consent to BRAF V600 mutation testing before randomization.

3. Tumor tissue available for PD-L1 testing at central lab or local laboratory; results must be obtained prior to randomization. In the event when archived tumor tissue is not available, new tumor biopsy or historical PD-L1 test results may be used for randomization, however tumor tissue, either taken previously or newly acquired, must be provided for central biomarker confirmation for final data analyses.

   PD-L1 expression level is required for randomization. In order to be randomized, a patient must be classified as PD-L1 positive or PD-L1 negative according to the following criteria:

   • PD-L1 positive (≥ 1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells) vs
   • PD-L1 negative (< 1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells).

   Note: If an insufficient amount of tumor tissue is available prior to the start of the screening phase, patients must consent to allow the acquisition of additional tumor tissue for performance of biomarker analyses.

4. Males or females 12 years of age or older.

5. ECOG performance status ≤1 for age ≥18 years, Lansky performance status ≥80% for age 12 to 17 years.

6. At least one measurable lesion defined by RECIST 1.1 criteria, (separate from the lesion to be used for tumor tissue collection) not counting brain metastasis with:

   • Longest diameter ≥10 mm by CT (when slice thickness is ≤5 mm); or ≥ 2× slice thickness (when slice thickness is >5 mm)
   • Pathologically enlarged lymph node: ≥15 mm in short axis by CT (when slice thickness is ≤5 mm)
   • Clinical: ≥10 mm (that can be accurately measured with calipers).

7. Have not received anti-PD-1, anti-PD-L1 or other systemic therapy for unresectable or metastatic melanoma, except for the following, provided that the patient has recovered from all treatment-related toxicities:

   • BRAF mutation targeting therapy > 4 weeks before administration of Study Treatment.
   • Adjuvant or neoadjuvant therapy with PD-1 or PD-L1 inhibitors or anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) is allowed if disease progression/or recurrence had occurred at least 6 months after the last dose of neoadjuvant/adjuvant therapy and prior to receiving the first dose on this study and no clinically significant immune related toxicities leading to treatment discontinuation were observed
   • Adjuvant interferon therapy must have been completed > 6 weeks before administration of Study Treatment

8. Any prior radiotherapy or minor surgery must be completed at least 2 weeks and 1 week respectively before Day 1 dosing and recovered from all treatment related toxicities

9. Screening laboratory results within 14 days prior to randomization:

   • Hematology: WBC ≥3000/μL, neutrophils ≥1500/μL, platelets ≥100 × 103/μL, hemoglobin ≥10.0 g/dL independent of transfusion. The use of erythropoietic growth factor to achieve hemoglobin (Hgb) ≥ 10 g/dl is acceptable.
   • The CrCL≥ 30 mL/min using Cockcroft-Gault formula.
   • AST and ALT ≤3 × ULN, alkaline phosphatase ≤2.5 × ULN unless bone metastases present (patients with documented bone metastases: alkaline phosphatase <5 x ULN), bilirubin ≤ 1.5 × ULN (unless known Gilbert's disease where it must be ≤ 3 × ULN), serum albumin ≥ 3.0 g/dL).

10. Negative serum pregnancy test at baseline for women of childbearing potential.

11. Females of childbearing potential (non-surgically sterile or premenopausal female capable of becoming pregnant) and all males (due to potential risk of drug exposure through the ejaculate) must agree to use adequate birth control measures from study start, during the study and for 5 months after the last dose of Study Drug. Acceptable methods of birth control in this trial include two highly effective methods of birth control (as determined by the Investigator; one of the methods must be a barrier technique) or abstinence.

12. Have the ability to understand and the willingness to sign a written informed consent document, comply with study scheduled treatment, visits and assessments.

Exclusion Criteria

1. History of ≥ Grade 3 hypersensitivity reactions to monoclonal antibodies.

2. Previous treatment with a PD-1, PD-L1, PD-L2, CTLA-4 inhibitor, or any other agents targeting T-cell co-stimulation or immune checkpoint pathways for unresectable or metastatic melanoma.

3. Recipient of solid organ transplant.

4. History of a cardiovascular illness including: congestive heart failure (New York Heart Association Grade III or IV); unstable angina or myocardial infarction within the previous 6 months prior to first dose of Study Treatment; or symptomatic cardiac arrhythmia despite medical management. QT interval corrected by heart rate using QTcF >450 ms in males or >470 ms in females, or congenital long QT syndrome.

5. Uncontrolled hypertension, systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg.

6. Patients with new, active, or progressive brain metastases or leptomeningeal disease with except when considered for a separate special open-label cohort.

7. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer, or bowel resection that affects absorption of orally administered drugs.

8. Active, known, or suspected autoimmune disease, except for Type I diabetes mellitus, hypothyroidism requiring only hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy.

9. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.

10. Known history of testing positive for HIV, known AIDS.

11. Hepatitis B surface antigen positive or hepatitis C antibody positive. Further investigation per institutional practices may be performed to exclude active infection.

12. Patients with a condition requiring chronic systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before administration of Study Treatment. Inhaled or topical steroids, or adrenal replacement dose of corticosteroids at dose ≤ 10 mg/day prednisone equivalent are permitted.

13. Use of another investigational agent (drug or vaccine not marketed for any indication) within 28 days or before administration of Study Treatment. If the investigational agent is a monoclonal antibody then within 3 months before administration of Study Treatment

14. Pregnant or breast-feeding women.

15. Have a history of any other malignancy unless in remission for 2 years or locally curable cancers that have been treated with curative intent with no evidence of recurrence, such as:

    • Basal or squamous cell skin cancer
    • Superficial bladder cancer
    • Carcinoma in situ of cervix or breast
    • Incidental prostate cancer
    • Non melanomatous skin cancer
    • Prostate cancer treated with curative intent with serum prostate specific antigen (PSA) < 2.0 ng/mL

16. Patients with medical conditions requiring administration of strong cytochrome P450 (CYP), CYP3A4 Inducers and Inhibitors with no alternative therapy.

17. Uncontrolled adrenal insufficiency or active chronic liver disease.

18. Has received approved live vaccine/live attenuated vaccines within 30 days of planned Cycle 1 Day 1. Inactivated viral vaccines or vaccines based upon subviral component are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are not allowed. COVID-19 vaccination should be administered at least 7 days before Cycle 1 Day 1.

19. Underlying medical conditions that, in the Investigator's opinion, will make the administration of Study Treatment hazardous or obscure the interpretation of toxicity determination or AEs.

20. Patients with a history of or active interstitial lung disease (ILD) or non-infectious pneumonitis.

21. Patients with prior organ or hematopoietic cell transplant (HCT), including allogeneic HCT.

22. Patients with known sensitivity to any of the ingredients of the Study Treatment.

23. Patients who received radiation therapy within 14 days of the first dose of the Study Treatment.

24. Patients who take drugs that prolong the QT interval or cause torsades de pointes or produce significant ventricular dysrhythmias.

25. Patients that are unwilling or unable to comply with procedures required in this protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Test Arm	HBI-8000 in combination with nivolumab	HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days
Control Arm	Placebo in combination with nivolumab	Placebo oral BIW + nivolumab IV at specific doses on specific days

Primary Outcome Measures

Name	Time	Method
Primary Outcome	From date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months	Progression-free Survival (PFS) defined as the time (in days) from the date of randomization to the first date of documented disease progression as determined by BIRC, or the date of death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months	Objective Response Rate (ORR) defined as the percentage of patients enrolled in each study arm with a best response of Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the blinded independent review committee (BIRC).
Overall Survival	From date of randomization to death due to any cause, assessed up to 48 months	Overall Survival (OS) defined as the time from randomization date to the date of death due to any cause.
Safety, defined as the incidence rate of AEs	From date of screening until the end of study, assessed up to 48 months	Safety, defined as the incidence rate of AEs. The NCI-CTCAE v5.0 will serve as the reference document for choosing the appropriate terminology to grade the severity of AEs, and to assess the causal relationship and outcomes.

Trial Locations

Locations (139)

Cape Town Oncology Trials Cape Gate Oncology Centre; 🇿🇦 Kraaifontein, Western Cape, South Africa

Univ.-Lkinik für Dermatologie, Venerologie und Allergologie; 🇦🇹 Innsbruck, Austria

Cliniques Universitaires; 🇧🇪 Brussels, Belgium

Jessa Ziekenhuis; 🇧🇪 Hasselt, Belgium

Clinique Saint-Pierre; 🇧🇪 Ottignies, Belgium

Hospital São Vicente de Paulo; 🇧🇷 Centro, Rio Grande Do Sul, Brazil

Oncosite-Centro de Pesquisa Clίnica em Oncologia; 🇧🇷 São Cristóvão, Rio Grande Do Sul, Brazil

Hospital Bruno Born; 🇧🇷 Lajeado, Rio Grande Do Sul, Brazil

Memorial Regional Hospital; 🇺🇸 Hollywood, Florida, United States

Comprehensive Blood and Cancer Center; 🇺🇸 Bakersfield, California, United States

Kaiser Permanente Oncology Research; 🇺🇸 Riverside, California, United States

Hospital do Câncer de Londrina; 🇧🇷 Londrina, Paraná, Brazil

The Medical Oncology Centre of Rosebank; 🇿🇦 Johannesburg, Gauteng, South Africa

Frederick Memorial Healthcare System; 🇺🇸 Frederick, Maryland, United States

Baptist MD Anderson Cancer Center; 🇺🇸 Jacksonville, Florida, United States

Boca Raton Regional Hospital, Lynn Cancer Institute; 🇺🇸 Boca Raton, Florida, United States

Gabrail Cancer Center Research; 🇺🇸 Canton, Ohio, United States

Baptist Health Lexington; 🇺🇸 Lexington, Kentucky, United States

Southeastern Medical Oncology Center; 🇺🇸 Goldsboro, North Carolina, United States

Toledo Clinic Cancer Center; 🇺🇸 Toledo, Ohio, United States

Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Medisearch Clinical Trials; 🇺🇸 Saint Joseph, Missouri, United States

Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

St Louis Cancer Care; 🇺🇸 Bridgeton, Missouri, United States

Renovatio Clinical; 🇺🇸 The Woodlands, Texas, United States

St. Elizabeth Healthcare; 🇺🇸 Edgewood, Kentucky, United States

Hopital de Câncer de Barretos-Fundação Pio XII; 🇧🇷 Barretos, Sao Paulo, Brazil

CHU de Besançon - Hôpital Jean MINJOZ; 🇫🇷 Besançon, France

CHU Grenoble Alpes; 🇫🇷 La Tronche, France

Charite Universitaetsmedizin Berlin - Campus Charite Mitte; 🇩🇪 Berlin, Germany

A.O.S. Maria della Misericordia, Oncologia Medica; 🇮🇹 Perugia, Italy

Instituto do Cancer do Estado de São Paulo - "Octavio Frias de Oliveira"-ICESP; 🇧🇷 São Paulo, Brazil

CHU de Dijon, Service de dermatologie; 🇫🇷 Dijon, France

Chonnam National University Hwasun Hospital; 🇰🇷 Hwasun, Jeollanam-do, Korea, Republic of

National Hospital Organization Kyushu Cancer Center; 🇯🇵 Fukuoka, Japan

CEPHO-Centro de Estudos e Pesquisas de Hematologia e Oncologia; 🇧🇷 Santo André, São Paulo,, Brazil

Fakultni nemocnice Kralovske Vinohrady; 🇨🇿 Prague, Czechia

IRCCS Giovanni Paolo II Oncologia Medica; 🇮🇹 Bari, Italy

Carolina Blood and Cancer Care Associates; 🇺🇸 Lancaster, South Carolina, United States

Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone - U.O. Oncologia Medica; 🇮🇹 Palermo, Italy

A.O.U Senese Policlinico Santa Maria alle Scotte-UOC Immunoterapia Oncologica; 🇮🇹 Siena, Italy

Vivantes Klinikum Spandau, Dermatologie und Allergologie; 🇩🇪 Berlin, Germany

Hospital de Clίnίcas de Porto Alegre; 🇧🇷 Santa Cruz Do Sul, Rio Grande Do Sul, Brazil

Universitaetsklinikum Schleswig Holstein - Campus Luebeck; 🇩🇪 Luebeck, Germany

Humanitas Istituto Clinico Catanese, U.O. Oncologia Medica; 🇮🇹 Misterbianco, Italy

Centro Gaúcho Integrado de Oncologia, Hematologia; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Hôpital Saint-Louis; 🇫🇷 Paris, France

Istituto Nazionale Tumori Fondazione G. Pascale, Oncologia Medica e Terapia Innovativa; 🇮🇹 Napoli, Italy

Policlinico G.B. Rossi-Borgo Roma-Centro Ricerche Cliniche di Verona; 🇮🇹 Verona, Italy

Fakultni nemocnice Ostrava Kozni oddeleni; 🇨🇿 Ostrava-Poruba, Czechia

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Universitaetsklinikum Heidelberg, NCT-Dermatoonkologie; 🇩🇪 Heidelberg, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz, Hautklinik; 🇩🇪 Mainz, Germany

CHRU Lille - Hôpital Claude Huriez, Clinique de Dermatologie; 🇫🇷 Lille, France

Ensino e Terapia de Inovação Clίnica AMO-ETICA; 🇧🇷 Salvador, Bahia, Brazil

Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie; 🇩🇪 Leipzig, Germany

Universitaetsklinikum Koeln, Dermatologie und Venerologie,; 🇩🇪 Koeln, Germany

Shinshu University Hospital; 🇯🇵 Matsumoto, Nagano, Japan

Studienzentrum Dermao-Onkologie, Universitaetsklinikum Tuebingen; 🇩🇪 Tuebingen, Germany

Fakultni nemocnice Olomoue; 🇨🇿 Olomouc, Czechia

Hôpital La Timone; 🇫🇷 Marseille, France

Royal Brisband and Women's Hospital; 🇦🇺 Brisbane, Australia

Okayama University Hospital; 🇯🇵 Okayama, Japan

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, Italy

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS; 🇮🇹 Bologna, Italy

National Hospital Organization Osaka National Hospital; 🇯🇵 Chuo Ku, Osaka, Japan

Shizuoka Cancer Center; 🇯🇵 Nagaizumi-cho, Sunto-gun, Japan

Helios Klinikum Erfurt, Dermatologie und Allergologie; 🇩🇪 Erfurt, Germany

Universitaetsklinikum Freiburg, Klinik fuer Dermatologie und Venerologie; 🇩🇪 Freiburg, Germany

National Cancer Centre; 🇸🇬 Singapore, Singapore

Niigata Cancer Center Hospital; 🇯🇵 Niigata, Japan

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Nuffield Health Wessex Hospital; 🇬🇧 Eastleigh, Hampshire, United Kingdom

Hospital Regional Universitario de Málaga; 🇪🇸 Málaga, Spain

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, Spain

Severance Hospital Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Ballarat Health Services; 🇦🇺 Ballarat, Victoria, Australia

University of the Sunshine Coast; 🇦🇺 Buderim, Queensland, Australia

Icon Cancer Centre Wesley; 🇦🇺 South Brisbane, Queensland, Australia

Goulburn Valley Health; 🇦🇺 Shepparton, Victoria, Australia

Liverpool Hospital; 🇦🇺 Liverpool, Australia

Osaka Prefectural Hospital Organization Osaka International Cancer Institute; 🇯🇵 Osaka, Japan

Utah Cancer Specialists; 🇺🇸 Salt Lake City, Utah, United States

Innovative Clinical Research Institute (ICRI); 🇺🇸 Pasadena, California, United States

California Cancer Associates for Research and Excellence, Inc. (cCARE); 🇺🇸 San Marcos, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Emad Ibrahim, MD, INC; 🇺🇸 Redlands, California, United States

Ascension Sacred Heart Medical Oncology; 🇺🇸 Pensacola, Florida, United States

Thomas Jefferson University Medical Oncology Clinic; 🇺🇸 Philadelphia, Pennsylvania, United States

AnMed Health; 🇺🇸 Anderson, South Carolina, United States

Sydney Adventist Hospital; 🇦🇺 Wahroonga, New South Wales, Australia

Inova Schar Cancer Institute; 🇺🇸 Fairfax, Virginia, United States

Affinity Clinical Research; 🇦🇺 Nedlands, Australia

Calvary Mater Newcastle; 🇦🇺 Waratah, Australia

Tweed Hospital; 🇦🇺 Tweed Heads, Australia

Medical University of Graz Department of Dermatology and Venerology; 🇦🇹 Graz, Austria

Hôpital Ambroise Paré; 🇫🇷 Boulogne-Billancourt, France

CHU de Rouen-Hôpital; 🇫🇷 Rouen, France

Institut Gustave Roussy, Service de Dermatologie; 🇫🇷 Villejuif, France

Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie; 🇩🇪 Dresden,, Germany

Universitatsklinikum Essen Klinik fur Dermatologie Studienambulanz; 🇩🇪 Essen, Germany

Fondazione IRCCS CA'Granda Ospedale Maggiore Policlinico-Oncologia Medica; 🇮🇹 Milan, Milano, Italy

Universitaetsklinikum Mannheim, Klinik f. Dermatologie, Venerologie, Allergologle,; 🇩🇪 Mannheim, Germany

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milan, Milano, Italy

The Cancer Institute Hospital of JFCR; 🇯🇵 Koto-Ku, Tokho, Japan

National Cancer Center; 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of

Tauranga Hospital; 🇳🇿 Tauranga, New Zealand

Severance Hospital Younsei University Health System,; 🇰🇷 Seoul, Gyeonggi, Korea, Republic of

Cha University Bundang Medical Center; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, New Zealand

Chungnam National University Hospital; 🇰🇷 Daejeon, Jung-gu, Korea, Republic of

Hospial Oncologico, Puerto Rico Medical Center; 🇵🇷 Rio Piedras, Puerto Rico

Wilgers Oncology Centre; 🇿🇦 Pretoria, Gauteng, South Africa

Curo Oncology; 🇿🇦 Pretoria, Gauteng, South Africa

West Rand Oncology Centre Flora Clinic; 🇿🇦 Roodepoort, Gauteng, South Africa

Catalan Institute of Oncology; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

ICO Badalona-Hospital Universitari Germans Trias I Pujol; 🇪🇸 Barcelona, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

MD Anderson Cancer Center; 🇪🇸 Madrid, Spain

Hospital Universitario Fundación Jimenez Diaz; 🇪🇸 Madrid, Spain

Centro Integral Oncologico Clara Campal; 🇪🇸 Madrid, Spain

Edinburgh Cancer Center Western General Hospital; 🇬🇧 Edinburgh, United Kingdom

Hospital Universitario Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer,; 🇧🇷 Curitiba, Paraná, Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto; 🇧🇷 São José Do Rio Preto, São Paulo, Brazil

Hospital de la Citadelle; 🇧🇪 Liège, Belgium

Fundação Doutor Amaral Carvalho; 🇧🇷 Jaú, São Paulo, Brazil

AZ Klina; 🇧🇪 Brasschaat, Belgium

AZ Maria Middelares; 🇧🇪 Ghent, Belgium

Cancercare Rondebosch Oncology; 🇿🇦 Rondebosch, Western Cape, South Africa

Orlando Health; 🇺🇸 Orlando, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

AMR Kansas City; 🇺🇸 Kansas City, Missouri, United States

Froedtert Hospital, Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

St. Vincent - Frontier Cancer Center; 🇺🇸 Billings, Montana, United States

Excellentis Clinical Trial Consultants; 🇿🇦 George, Western Cape, South Africa