A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
- Conditions
- Lymphoma, Large B-Cell, DiffuseLymphoma, FollicularCarcinoma, Squamous Cell of Head and NeckLymphoma, Non-HodgkinCarcinoma, Non-Small-Cell LungCarcinoma, Renal CellMalignant Melanoma
- Interventions
- Registration Number
- NCT01307267
- Lead Sponsor
- Pfizer
- Brief Summary
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 190
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Portion B rituximab PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma Portion A PF-05082566 PF-05082566 single agent in patients with advanced cancer Portion B PF-05082566 PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
- Primary Outcome Measures
Name Time Method Number of Participants With DLTs in First 2 Cycles of Portion B Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days) DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days) DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
- Secondary Outcome Measures
Name Time Method Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A Up to approximately 2 years Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells. The abnormalities with at least 1 participant are presented here.
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A Up to approximately 2 years Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. The abnormalities with at least 1 participant are presented here.
PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A Day 1 pre-dose of Cycle 2 Ctrough of PF-05082566 was observed directly from data.
PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose. AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Objective response: confirmed best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST version 1.1. BOR of CR: target lesions and non-target diseases achieved CR, without new lesions. BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-progression of disease (non-PD), indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and \>=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose Cmax of PF-05082566 was observed directly from data.
PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose. AUClast of PF-05082566 was determined by linear/log trapezoidal method.
Overall Survival in Portion A Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B Up to approximately 2 years Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells. The abnormalities with at least 1 participant are presented here.
PF-05082566 Tmax in Portion B Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose. Tmax of PF-05082566 was observed directly from data as time of Cmax.
PF-05082566 Clearance (CL) in Portion A Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose. CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2. It was reported in units of milliliter per hour per kilogram (mL/hr/kg).
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A Up to approximately 2 years An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both non-serious AEs and SAEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Causality of AEs was determined by the investigator.
Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A Up to approximately 2 years An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A Up to approximately 2 years For vital signs in Portion A, blood pressure and pulse rate were measured. Clinical significance was determined by the investigator.
PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose. Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A Up to approximately 2 years ADA for PF-05082566 was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer\>=6.23.
Progression-Free Survival in Portion A Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Progression-free survival: the time from Cycle 1 Day 1 to the date of the first documentation of objective PD or death due to any cause, whichever occurred first. Objective PD per RECIST version 1.1: \>=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
PF-05082566 Cmax in Portion B Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose. Cmax of PF-05082566 was observed directly from data.
PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose. Tmax of PF-05082566 was observed directly from data as time of Cmax.
PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose. AUCinf = AUClast + (Clast\*/kel), where Clast\* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A Up to approximately 2 years Categorical summarization criteria for QTc interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate): 1) absolute value of \>450 to \<=480 milliseconds (msec), \>480 to \<=500 msec, \>500 msec; 2) a maximum change from baseline of \>30 to \<=60 msec or \>60 msec.
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B Up to approximately 2 years Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. The abnormalities with at least 1 participant are presented here.
PF-05082566 AUCinf in Portion B Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose. AUCinf = AUClast + (Clast\*/kel), where Clast\* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
Rituximab Cmax and Ctrough in Portion B Day 1 pre-dose of Cycle 2 Cmax and Ctrough of rituximab were observed directly from data.
Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B Up to approximately 4 years An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B Up to approximately 2 years For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured. Clinical significance was determined by the investigator.
PF-05082566 Ctrough in Portion B Day 1 pre-dose of Cycle 2 Ctrough of PF-05082566 was observed directly from data.
PF-05082566 AUClast in Portion B Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose. AUClast of PF-05082566 was determined by linear/log trapezoidal method.
PF-05082566 Vss in Portion B Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose. Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B Up to approximately 2 years Categorical summarization criteria for QTc interval: 1) absolute value of \>450 to \<=480 milliseconds (msec), \>480 to \<=500 msec, \>500 msec; 2) a maximum change from baseline of \>30 to \<=60 msec or \>60 msec.
Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Objective Response in Portion B was defined as BOR of CR or PR according to Cheson 2007 criteria. BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or \>=50% decrease in the sum of the product diameters \[SPD\] of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion \>=15 mm in greatest transverse diameter \[GTD\], unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
Duration of Response in Portion A Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Duration of response: the time from first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1) to the date of first documentation of objective progression of disease (PD) or death due to any cause. Objective PD per RECIST version 1.1: \>=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeters (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions. This outcome measure reports the individual values for evaluable participants (instead of medians etc) due to the limited number of events.
Time to Response in Portion A Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Time to response: the time from Cycle 1 Day 1 to the first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1). BOR of CR: target lesions and non-target diseases achieved CR, without new lesions. BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes decreased to normal size); PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and \>=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
Number of Participants With Treatment-Emergent AEs and SAEs in Portion B Up to approximately 4 years An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both non-serious AEs and SAEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Causality of AEs was determined by the investigator.
Duration of Response in Portion B Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Duration of Response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from first documentation of objective response to the date of first documentation of objective PD or death due to any cause. Objective PD per Cheson 2007 was defined as: PD of index lesions (\>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion \>=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
PF-05082566 AUCtau in Portion B Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose. AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
PF-05082566 CL in Portion B Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose. CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.
Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B Up to approximately 2 years ADA for PF-05082566 and rituximab was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer\>=6.23. Positive ADA for rituximab: titer\>=1.88.
Progression-Free Survival in Portion B Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Progression-free survival in Portion B was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective PD (per Cheson 2007) or death due to any cause, whichever occurred first. Objective PD per Cheson 2007 was defined as: PD of index lesions (\>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion \>=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
Overall Survival in Portion B Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Time to Response in Portion B Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years) Time to response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from Cycle 1 Day 1 to the first documentation of objective response. BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or \>=50% decrease in the SPD of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion \>=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
Trial Locations
- Locations (39)
City of Hope
🇺🇸Duarte, California, United States
UC San Diego Moores Cancer Center-Investigational Drug Services
🇺🇸La Jolla, California, United States
UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
🇺🇸La Jolla, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Georgetown University Medical Center Department of Pharmacy, Research
🇺🇸Washington, District of Columbia, United States
UC San Diego Medical Center - Hillcrest
🇺🇸San Diego, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Siteman Cancer Center-West County
🇺🇸Creve Coeur, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Washington University Infusion Center Pharmacy
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center- South County
🇺🇸Saint Louis, Missouri, United States
The University of Texas - M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Siteman Cancer Center - St. Peters
🇺🇸Saint Peters, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Centre d'investigation clinique
🇫🇷RENNES cedex 9, France
South Texas Accelerated Research Therapeutics, LLC
🇺🇸San Antonio, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
🇮🇹Bologna, BO, Italy
Ospedale San Raffaele di Milano
🇮🇹Milano, MI, Italy
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Akita University Hospital
🇯🇵Akita, Japan
Research Administration Office: Clinical Research Unit
🇺🇸Los Angeles, California, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Ronald Reagan UCLA Medical Center, Drug Information Center
🇺🇸Los Angeles, California, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
UCLA Bowyer Clinic
🇺🇸Los Angeles, California, United States
Santa Monica UCLA Hematology & Oncology Clinic
🇺🇸Santa Monica, California, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
UCLA Hematology-Oncology Clinic
🇺🇸Los Angeles, California, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
The Emory Clinic, Building A
🇺🇸Atlanta, Georgia, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Brigham and Woman's Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
🇯🇵Tokyo, Japan
University of Washington Medical Center
🇺🇸Seattle, Washington, United States