A Phase 1/2 Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma

Phase 1

Completed

• Conditions: Follicular Lymphoma; Non-Hodgkin Lymphoma
• Interventions: Drug: 15 MBq/kg Betalutin; Drug: 20 MBq/kg Betalutin; Drug: 10 MBq/kg Betalutin; Drug: 40 mg lilotomab; Drug: Rituximab; Drug: 100 mg/m2 lilotomab; Drug: 60 mg/m2 lilotomab; Drug: 12.5 mBq/kg Betalutin

• Registration Number: NCT01796171
• Lead Sponsor: Nordic Nanovector

Brief Summary

This study is a Phase 1/2 open-label three part study in patients with relapsed indolent Non-Hodgkin's lymohoma (NHL) (Parts A and C) or relapsed/refractory follicular lymphoma (FL) (Part B).

Detailed Description

Part A of the study was a Phase 1/2a study to assess the safety and preliminary efficacy of different treatment regimens of Betalutin with expansion at the candidate recommended Phase 2 doses. Part B was a dedicated Phase 2b randomized substudy to further assess the efficacy and safety of the candidate recommended Phase II doses. Part C was a Phase 2a fixed dose expansion cohort planned to obtain supplementary pharmacokinetic data.

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2013-02-19
• Study First Submitted QC: 2013-02-19
• Study First Posted: 2013-02-21
• Primary Completion: 2022-10-25
• Study Completion: 2022-10-27
• Results First Submitted: 2023-03-31
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-18
• Results First Posted: 2024-01-10
• Last Update Submitted: 2024-06-19
• Last Update Posted: 2024-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 191

Inclusion Criteria

1. Histologically confirmed (by World Health Organization [WHO] classification) relapsed incurable non-Hodgkin B-cell lymphoma of following subtypes; follicular grade I-IIIA (for Part C, this excludes patients meeting Part B criteria, who should enter Part B), marginal zone, small lymphocytic, lymphoplasmacytic, mantle cell.

2. Age ≥ 18 years.

3. Part A: A pre-study WHO performance status of 0-1; Part C: WHO performance status of 0-2.

4. Life expectancy should be ≥3 months.

5. <25% tumour cells in bone marrow biopsy (biopsy taken from a site not previously irradiated).

6. Measurable disease by radiological methods.

7. Women of childbearing potential must:

   1. understand that the study medication is expected to have teratogenic risk.
   2. have a negative pregnancy test.
   3. agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea.

8. Male patients must agree to use condoms during intercourse throughout study medication therapy and the following 12 months.

9. Patients previously treated with native rituximab are eligible.

10. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow up visits and examination.

11. The patient has been fully informed about the study and has signed the informed consent form.

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Exclusion Criteria

Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, uncontrolled asthma/allergy requiring systemic steroids, known to be human immunodeficiency virus (HIV) positive.

2. Laboratory values within 15 days pre-registration:

3. Absolute neutrophil counts (ANC) ≤1.5×109/L.

4. Part A: Platelet count ≤150×109/L; Part C: Platelet count <150×109/L. For Part C, criteria 2a and 2b must be satisfied within 72 hours of the administration of rituximab

5. Total bilirubin ≥30 mmol/L (Part A only). Total bilirubin > 1.5×ULN (except patients with documented Gilbert's syndrome [≥3.0 mg/dL]) (Part C only).

6. Alkaline phosphatase (ALP) and alanine transaminase (ALT) ≥4×normal level (Part A only).

   Aspartate transaminase (AST), ALT or ALP >2.5×ULN (or >5.0×ULN with liver involvement by primary disease). (Part C only).

7. Creatinine ≥115 µmol/L (men), 97 µmol/L (women) (Part A only). Serum creatinine ≥1.5×ULN (Part C only).

8. Haemoglobin <9.0 g/dL (Part C only). 3. Known central nervous system (CNS) involvement of lymphoma. 4. Previous total body irradiation. 5. Positive test for human anti-murine antibody (HAMA) at screening. 6. Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study treatment. Pre treatment with rituximab is allowed.

   7. Pregnant or lactating women. 8. Previous hematopoietic stem cell transplantation (autologous and allogenic). 9. Part A: Previous treatment with radioimmunotherapy. Part C: Not applicable. 10. Actively participating in another study or received an IMP within 4 weeks prior to enrolment.

   8. Receipt of live-attenuated vaccine within 30 days prior to enrolment. 12. Part A and Part C: Test positive for hepatitis B (HBsAg and anti-HBc). Part C only: Test positive for hepatitis C and human immunodeficiency virus (HIV).

   9. A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin.

   Part B:

   Inclusion Criteria:

   Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL (grade I IIIA).

   2. Male or female aged ≥18 years. 3. Received at least 2 prior systemic anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy). Systemic regimens including agents such as idelalisib or other PI3K inhibitors qualify as a prior line of therapy.

   3. Prior therapy must have included a rituximab/anti-CD20 agent and an alkylating agent - which may be been administered in separate regimens.

   4. Patients must be refractory to any at least one previous regimen that contained rituximab or an anti CD20 agent, with refractoriness defined as:

i. no response (no CR or PR) during therapy, or ii. a response (CR/PR) lasting less than 6 months after the completion of a regimen including rituximab/anti-CD20 therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20 maintenance therapy, or within 6 months of completion of maintenance therapy).

6. WHO performance status of 0-2. 7. Life expectancy of ≥3 months. 8. Bone marrow tumour infiltration <25% (in biopsy taken from a site not previously irradiated).

7. Measurable disease by CT or MRI: longest diameter (LDi) >1.5 cm for nodal lesion, LDi >1.0 cm for extra nodal lesion on an assessment performed during the screening period.

Criteria 10 and 11 must be satisfied within 72 hours of the administration of rituximab:

10. ANC ≥1.5×109/L. 11. Platelet count ≥100×109/L.

Criteria 12 to 15 must be verified at time of eligibility review within 2 weeks prior to rituximab administration:

12. Haemoglobin ≥9.0 g/dL. 13. Total bilirubin ≤1.5×upper limit of normal (ULN) (except patients with documented Gilbert's syndrome [<3.0 mg/dL]).

13. Liver enzymes: AST; ALT or ALP ≤2.5×ULN (or ≤5.0×ULN with liver involvement by primary disease).

14. Adequate renal function as demonstrated by a serum creatinine <1.5×ULN. 16. Women of childbearing potential must:

15. understand that the study medication is expected to have teratogenic risk.

16. have a negative serum beta human-chorionic gonadotropin (ß-HCG) pregnancy test at screening.

17. commit to continued abstinence from heterosexual intercourse (excluding periodic abstinence or the withdrawal method) or begin a highly effective method of birth control with a Pearl-Index <1%, without interruption, from 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea. Apart from abstinence, highly effective methods of birth control are: i. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).

ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Vasectomised partner. 17. Male patients must agree to use condoms during intercourse throughout study treatment administration and for 12 months following administration of Betalutin.

18. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow up visits and examination.

19. The patient has been fully informed about the study and has signed the informed consent form.

20. Negative HAMA test at screening. 21. Negative test at screening for Hepatitis B (negative HBsAg and anti-HBc), Hepatitis C and HIV.

Exclusion Criteria

1. Prior hematopoietic allogenic stem cell transplantation.
2. Patients with a prior autologous SCT are excluded unless at least two years have elapsed since transplantation.
3. Evidence of histological transformation from FL to diffuse large B-cell lymphoma (DLBCL) at time of screening (transformation to grade IIIB that was successfully treated with recurrence of grade I-IIIA initial clone is accepted).
4. Previous total body irradiation.
5. Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other systemic agent including any investigational agent) within 4 weeks prior to start of study treatment (corticosteroid treatment at doses of ≤ 20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF] are permitted up to 2 weeks prior to start of rituximab)..
6. Patients who are receiving any other investigational medicinal products.
7. Patients with known or suspected CNS involvement of lymphoma.
8. History of malignancy other than FL within 5 years prior to screening( i.e. patients with cancer diagnosed within 5 years prior to screening or who were diagnosed prior to 5 years and were not in CR or were on treatment within 5 years prior to screening), with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.

.9. Pregnant or breastfeeding women. 10. Exposure to another CD37 targeting drug. 11. A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin.

12. Has received a live-attenuated vaccine within 30 days prior to enrolment. 13. Evidence of severe or uncontrolled systemic diseases:

13. Uncontrolled infection including evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment.

14. Pulmonary conditions e.g. unstable or uncompensated respiratory disease.

15. Hepatic, renal, neurological, or metabolic conditions - which in the opinion of the investigator would compromise the protocol objectives.

16. Psychiatric conditions e.g. patients unlikely to comply with the protocol, e.g. mental condition rendering the patient unable to understand the nature, scope, and possible consequences of participating in the study.

17. History of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome.

18. Cardiac conditions in the previous 24 weeks (before date of consent), including

i. history of acute coronary syndromes (including unstable angina). ii. class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.

iii. known uncontrolled arrhythmias (except sinus arrhythmia).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A, Arm 1: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing	15 MBq/kg Betalutin	15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part A, Arm 1: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing	40 mg lilotomab	15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part A, Arm 1: 20 MBq/kg Betalutin with lower dose lilotomab pre-dosing	20 MBq/kg Betalutin	20 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part A, Arm 1: 20 MBq/kg Betalutin with lower dose lilotomab pre-dosing	40 mg lilotomab	20 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part A, Arm 2: 10 MBq/kg Betalutin with no pre-dosing	10 MBq/kg Betalutin	10 MBq/kg (based on body weight) Betalutin without pre-dosing
Part A, Arm 2: 15 MBq/kg Betalutin with no pre-dosing	15 MBq/kg Betalutin	15 MBq/kg (based on body weight) Betalutin without pre-dosing
Part A, Arm 3: 15 MBq/kg Betalutin with rituximab pre-dosing	15 MBq/kg Betalutin	15 MBq/kg (based on body weight) Betalutin with rituximab pre-dosing
Part A, Arm 3: 15 MBq/kg Betalutin with rituximab pre-dosing	Rituximab	15 MBq/kg (based on body weight) Betalutin with rituximab pre-dosing
Part A, Arm 4: 15 MBq/kg Betalutin with higher dose lilotomab pre-dosing	100 mg/m2 lilotomab	15 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing
Part A, Arm 5: 20 MBq/kg Betalutin with intermediate dose lilotomab pre-dosing	20 MBq/kg Betalutin	20 MBq/kg (based on body weight) Betalutin with 60 mg/m2 (based on body surface area) lilotomab pre-dosing
Part A, Arm 4: 20 MBq/kg Betalutin with higher dose lilotomab pre-dosing	20 MBq/kg Betalutin	20 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing
Part A, Arm 4: 20 MBq/kg Betalutin with higher dose lilotomab pre-dosing	100 mg/m2 lilotomab	20 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing
Part A, Arm 5: 20 MBq/kg Betalutin with intermediate dose lilotomab pre-dosing	60 mg/m2 lilotomab	20 MBq/kg (based on body weight) Betalutin with 60 mg/m2 (based on body surface area) lilotomab pre-dosing
Part B, Arm 2: 20 MBq/kg Betalutin with higher dose lilotomab pre-dosing	100 mg/m2 lilotomab	20 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing
Part B, Arm 3: 12.5 MBq/kg Betalutin with lower dose lilotomab pre-dosing	40 mg lilotomab	12.5 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part B, Arm 3: 12.5 MBq/kg Betalutin with lower dose lilotomab pre-dosing	12.5 mBq/kg Betalutin	12.5 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part C: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing	15 MBq/kg Betalutin	15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part A, Arm 1: 10 MBq/kg Betalutin with lower dose lilotomab pre-dosing	40 mg lilotomab	10 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part B, Arm 2: 20 MBq/kg Betalutin with higher dose lilotomab pre-dosing	20 MBq/kg Betalutin	20 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing
Part B, Arm 1: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing	15 MBq/kg Betalutin	15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part B, Arm 1: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing	40 mg lilotomab	15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part A, Arm 1: 10 MBq/kg Betalutin with lower dose lilotomab pre-dosing	10 MBq/kg Betalutin	10 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Part A, Arm 4: 15 MBq/kg Betalutin with higher dose lilotomab pre-dosing	15 MBq/kg Betalutin	15 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing
Part C: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing	40 mg lilotomab	15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing

Primary Outcome Measures

Name	Time	Method
Part A, Phase I	12 weeks	Number of participants with dose limiting toxicities (DLTs) in Part A
Part A, Phase IIa	5 years	Tumour response rates in patients in Part A receiving Betalutin based on evaluation of CT scan images including PET/CT imaging (and bone marrow biopsy if applicable).
Part B, Phase IIb	up to 5 years	Overall response rate in Part B defined as the number of participants with a best response of complete remission or partial remission at any time

Trial Locations

Locations (96)

FNsP Ostrava; 🇨🇿 Ostrava-Poruba, Czechia

Hacettepe University Oncology Hospital; 🇹🇷 Ankara, Turkey

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

West Penn Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University Of Arkansas For Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Ochsner Clinic Foundation; 🇺🇸 New Orleans, Louisiana, United States

Royal Hobart Hospital; 🇦🇺 Hobart, Australia

Hôpital Saint Louis; 🇫🇷 Paris, France

St James's Hospital; 🇮🇪 Dublin, Ireland

Institut Bergonie; 🇫🇷 Bordeaux, France

Baylor College of Medicine; 🇺🇸 Dallas, Texas, United States

Medizinische Universitaet Innsbruck; 🇦🇹 Innsbruck, Austria

CH Jolimont; 🇧🇪 La Louvière, Belgium

Universita Degli Studi Di Firenze-Azienda Ospedaliero-Universitaria Careggi (AOUC); 🇮🇹 Firenze, Italy

Asaf Harofeh Medical Center; 🇮🇱 Be'er Ya'aqov, Israel

Hospital Universitario Puerta del Mar; 🇪🇸 Cadiz, Spain

Chonbuk National University Hospital; 🇰🇷 Jeonju, Korea, Republic of

Clinical Hospital Centre Zagreb; 🇭🇷 Zagreb, Croatia

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

Medizinische Universität Wien - AKH Wien, Universitaetsklinik fuer Innere Medizin I; 🇦🇹 Wien, Austria

Universitair Ziekenhuis Gent (UZ Gent); 🇧🇪 Gent, Belgium

London Health Sciences Centre; 🇨🇦 London, Canada

UZ Leuven; 🇧🇪 Leuven, Belgium

University Hospital Olomouc; 🇨🇿 Olomouc, Czechia

Sault Area Hospital; 🇨🇦 Sault Ste Marie, Canada

Helsinki University Hospital Comprehensive Cancer Center; 🇫🇮 Helsinki, Finland

Kantonsspital Graubünden; 🇨🇭 Chur, Switzerland

Centrum Onkologii; 🇵🇱 Warszawa, Poland

"Istituto di Ematologia ed Oncologia Medica "" L. & A. Seragnoli""-Policlinico S. Orsola Malpighi"; 🇮🇹 Bologna, Italy

Istituto Europeo di Oncologia (IEO); 🇮🇹 Milano, Italy

Cukurova Universitesi Tip Fakültesi, Ic Hastaliklari Anabilim Dali; 🇹🇷 Adana, Turkey

Istanbul Universitesi Istanbul Tip Fakultesi; 🇹🇷 Fatih, Turkey

Hospital Universitario Virgen Macarena; 🇪🇸 Seville, Spain

Haemek Medical Center; 🇮🇱 Afula, Israel

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

Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Ankara Onkoloji Egitim ve Arastirma Hastanesi; 🇹🇷 Ankara, Turkey

Princes Margaret Cancer Centre; 🇨🇦 Toronto, Canada

Complexo Hospitalario Universitario de Ourense; 🇪🇸 Ourense, Spain

Western General Hospital; 🇬🇧 Edinburgh, United Kingdom

Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) - Hopital Bretonneau; 🇫🇷 Tours, France

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

AP-HP La Pitié salpétrière; 🇫🇷 Paris, France

יHadassah Ein Karem Medical Center; 🇮🇱 Jerusalem, Israel

The Norwegian Radium Hospital; 🇳🇴 Oslo, Norway

St Olav Hospital; 🇳🇴 Trondheim, Norway

Chu Grenoble - Hopital Michallon; 🇫🇷 Grenoble, France

Orszagos Onkologiai Intezet, A-Belgyogyaszati Onkologiai Osztaly; 🇭🇺 Budapest, Hungary

Corporacio Sanitaria Parc Taulí; 🇪🇸 Barcelona, Spain

Rambam Health Care Campus (RHCC); 🇮🇱 Haifa, Israel

National University Hospital; 🇸🇬 Singapore, Singapore

Dorset Cancer Centre Poole Hospital; 🇬🇧 Poole, Dorset, United Kingdom

Pratia MCM Kraków; 🇵🇱 Krakow, Poland

Ankara Universitesi Tip Fakultesi Cebeci Hastanesi Ic; 🇹🇷 Ankara, Turkey

Ege Universitesi Tip Fakültesi; 🇹🇷 İzmir, Turkey

Ondokuz Mayis Universitesi; 🇹🇷 Samsun, Turkey

Hospital Universitario Doctor Peset; 🇪🇸 Valencia, Spain

Hospital Clinico Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Imperial College Healthcare NHS Trust, Hammersmith Hospital; 🇬🇧 London, United Kingdom

Bristol Haematology and Oncology Centre; 🇬🇧 Bristol, United Kingdom

Clinica Universidad De Navarra; 🇪🇸 Pamplona, Spain

Cancercentrum -Center of Oncology; 🇸🇪 Umeå, Sweden

University College London Hospitals Nhs Foundation Trust; 🇬🇧 London, United Kingdom

Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Aarhus Universitetshospital; 🇩🇰 Aarhus, Denmark

Odense Univerisity Hospital; 🇩🇰 Odense, Denmark

SS Antonio & Biagio and C. Arrigo Hospital; 🇮🇹 Alessandria, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS; 🇮🇹 Meldola, Italy

"Istituto Nazionale Tumori Fondazione G. Pascale"; 🇮🇹 Napoli, Italy

Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS; 🇮🇹 Reggio Emilia, Italy

AO Ordine Mauriziano di Torino; 🇮🇹 Torino, Italy

Gaziantep Universitesi Sahinbey Arastirma ve Uygulama; 🇹🇷 Şehitkamil, Turkey

Pacific Shores Medical Group; 🇺🇸 Long Beach, California, United States

Boca Raton Regional Hospital; 🇺🇸 Boca Raton, Florida, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Central Hospital Of Central Finland; 🇫🇮 Jyväskylä, Finland

Semmelweis Egyetem, I Belgyogyaszati Klinika, Hematologiai Osztaly; 🇭🇺 Budapest, Hungary

University Hospital Galway; 🇮🇪 Galway, Ireland

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

Bnai Zion Medical Center (BZMC); 🇮🇱 Haifa, Israel

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Republic of

Haukeland Universitetssjukehus; 🇳🇴 Bergen, Norway

Szpital Morski Im.Pck W Gdynia; 🇵🇱 Gdynia, Poland

Health Research Institute La Fe - Hospital La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario Puerta de Hierro de Majadahonda; 🇪🇸 Majadahonda, Spain

Eskisehir Osmangazi Universitesi Tip Fakultesi Ic Hastaliklar; 🇹🇷 Eskişehir, Turkey

Celal Bayar Universitesi Tip Fakultesi; 🇹🇷 Manisa, Turkey

Derriford Hospital; 🇬🇧 Plymouth, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

The Royal Marsden NHS Foundation Trust; 🇬🇧 Sutton, United Kingdom

University of California, San Francisco (UCSF); 🇺🇸 San Francisco, California, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States