A Study of Obinutuzumab, Polatuzumab Vedotin, and Lenalidomide in Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Phase 1

Completed

Conditions: Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Interventions: Drug: Lenalidomide
Drug: Obinutuzumab
Drug: Polatuzumab Vedotin
Drug: Rituximab

Registration Number: NCT02600897

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL), followed by post-induction treatment with obinutuzumab in combination with lenalidomide in participants with FL who achieve a complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 114

Inclusion Criteria

Age greater than or equal to (>/=) 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola + Len) treatment group: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
For rituximab in combination with polatuzumab vedotin and lenalidomide (R + Pola + Len) treatment group: R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in patients who are not eligible for autologous stem-cell transplantation or who have experienced disease progression following treatment with high-dose chemotherapy plus autologous stem-cell transplantation
Histologically documented CD20-positive B-cell lymphoma as determined by the local laboratory
fluorodeoxyglucose (FDG)-avid lymphoma (i.e., positron emission tomography (PET)-positive lymphoma)
At least one bi-dimensionally measurable lesion
Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential

Exclusion Criteria

Grade 3b follicular lymphoma
History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
Known CD20-negative status at relapse or progression
Central nervous system (CNS) lymphoma or leptomeningeal infiltration
Prior allogeneic stem-cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
Current use of systemic immunosuppressant(s), or prior anti-cancer therapy to include: lenalidomide, fludarabine, or alemtuzumab within 12 months; radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
Active infection
Positive for human immunodeficiency virus (HIV) or hepatitis B or C
Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
Poor hematologic, renal, or hepatic function
Pregnant or lactating women
Life expectancy less than (<) 3 months

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose-escalation Cohort: FL	Polatuzumab Vedotin	Participants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Dose-escalation Cohort: DLBCL	Lenalidomide	Participants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Dose-escalation Cohort: FL	Lenalidomide	Participants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Dose-escalation Cohort: FL	Obinutuzumab	Participants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Dose-escalation Cohort: DLBCL	Polatuzumab Vedotin	Participants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Dose-escalation Cohort: DLBCL	Rituximab	Participants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Expansion Cohort: FL	Obinutuzumab	Participants with R/R FL who received induction treatment with polatuzumab vedotin and lenalidomide, in addition to obinutuzumab and achieved CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 24-months maintenance regimen consisting of lenalidomide and obinutuzumab for first 12 months followed by obinutuzumab treatment for next 12 months. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.
Expansion Cohort: FL	Lenalidomide	Participants with R/R FL who received induction treatment with polatuzumab vedotin and lenalidomide, in addition to obinutuzumab and achieved CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 24-months maintenance regimen consisting of lenalidomide and obinutuzumab for first 12 months followed by obinutuzumab treatment for next 12 months. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.
Expansion Cohort: DLBCL	Lenalidomide	Participants with R/R DLBCL who received induction treatment with polatuzumab vedotin and lenalidomide in addition to rituximab and achieved CR or PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 6-month consolidation regimen consisting of lenalidomide and rituximab. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.
Expansion Cohort: DLBCL	Rituximab	Participants with R/R DLBCL who received induction treatment with polatuzumab vedotin and lenalidomide in addition to rituximab and achieved CR or PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 6-month consolidation regimen consisting of lenalidomide and rituximab. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Dose-Limiting Toxicities (DLTs)	Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase	A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of \> 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase \> 3 x baseline and an increase in direct bilirubin \> 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Percentages have been rounded off to the first decimal point.
Percentage of Participants With Adverse Events (AEs)	From study start up to end of study (Up to a maximum of 69 months)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Percentages have been rounded off to the first decimal point.
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)	CR at EOI was assessed by IRC according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)	CR at EOI was determined by IRC according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans	6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks)	OR was defined as percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes \& ELS with score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake\> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions;no new lesions \& no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. Partial response (PR) based on PET-CT was defined as partial MR in lymph nodes \& ELS with score of 4 or 5 with reduced uptake compared with baseline \& residual masses of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). Percentages have been rounded off up to the second decimal point.
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)	CR at EOI was assessed by Investigator according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)	CR at EOI was determined by Investigator according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)	OR was defined percentage of participants with CR or PR assessed by the investigator according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes \& ELS with score of 1, 2, 3 with or without residual mass on 5PS, where 1=no uptake above background 2=uptake ≤ mediastinum 3=uptake\> mediastinum but ≤ liver 4=uptake moderately \> liver 5=uptake markedly higher than liver and/or new lesions;no new lesions \& no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes \& ELS with score of 4 or 5 with reduced uptake compared with baseline \& residual masses of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline(diffuse uptake compatible with reactive changes from chemotherapy allowed). Percentages are rounded off.
Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)	OR was defined as the percentage of participants with CR or PR, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in the sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 28 days). Percentages have been rounded off to the first decimal point.
Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone	Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months)	BOR=CR/PR per CT per MLRC. Per MLRC, CR based on CT was defined as a complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. Percentages have been rounded off to the first decimal point.
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody	Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
Observed Plasma Lenalidomide Concentration	Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)	OR was defined as the percentage of participants with CR or PR, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in the sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Observed Serum Rituximab Concentration	Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months)
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)	Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
Observed Serum Obinutuzumab Concentration	Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)	1 cycle = 28 days
Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab	Baseline up to approximately 2 years after last dose (up to approximately 69 months)	The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result.
Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab	Baseline up to approximately 2 years after last dose (up to approximately 69 months)	The number of participants with positive results for HACAs, also called ADAs against rituximab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result.
Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin	Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months)	The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result.
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE	Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)

Trial Locations

Locations (28): Nottingham University Hospitals NHS Trust - City Hospital
🇬🇧
Nottingham, United Kingdom
Maidstone & Tonbridge Wells Hospital; Kent Oncology Center
🇬🇧
Maidstone, United Kingdom
Barking, Havering and Redbridge University Hospitals NHS Trust - Queen's Hospital
🇬🇧
Romford, United Kingdom
The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology
🇬🇧
Wolverhampton, United Kingdom
Texas Oncology San Antonio Medical Center
🇺🇸
San Antonio, Texas, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Hospital Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
🇺🇸
Marietta, Georgia, United States
University of Missouri/Ellis Fischel
🇺🇸
Columbia, Missouri, United States
NYU School of Medicine
🇺🇸
New York, New York, United States
Washington University; Wash Uni. Sch. Of Med
🇺🇸
Saint Louis, Missouri, United States
Rocky Mountain Cancer Centers, LLP
🇺🇸
Irving, Texas, United States
Texas Oncology-Tyler
🇺🇸
Irving, Texas, United States
Complejo Hospitalario de Navarra
🇪🇸
Pamplona, Navarra, Spain
Insititut Catala D'Oncologia
🇪🇸
Hospitalet de Llobregat, Barcelona, Spain
Hospital Clínic. Barcelona
🇪🇸
Barcelona, Spain
Hospital Clínico Málaga
🇪🇸
Málaga, Malaga, Spain
Clínica Universidad de Navarra
🇪🇸
Pamplona, Navarra, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Gregorio Marañon
🇪🇸
Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz.
🇪🇸
Madrid, Spain
Hospital La Fe
🇪🇸
Valencia, Spain
St James University Hospital
🇬🇧
Leeds, United Kingdom
Barts Hospital; Institute of Cancer
🇬🇧
London, United Kingdom
H. Universitario Leonor
🇪🇸
Madrid, Spain
University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary
🇬🇧
Leicester, United Kingdom
Sarah Cannon Research Institute
🇬🇧
London, United Kingdom
Royal Liverpool University Hospital
🇬🇧
Liverpool, United Kingdom