A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab

• ClinicalTrials.gov Identifier: NCT01307267
• Recruitment Status: Completed
• First Posted: March 2, 2011
• Results First Posted: March 17, 2020
• Last Update Posted: March 17, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 28, 2011
• First Posted Date: March 2, 2011
• Results First Submitted Date: January 31, 2020
• Results First Posted Date: March 17, 2020
• Last Update Posted Date: March 17, 2020
• Actual Study Start Date: June 21, 2011
• Actual Primary Completion Date: February 20, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2020)

• Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A [ Time Frame: 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.
• Number of Participants With DLTs in First 2 Cycles of Portion B [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: February 28, 2011): Dose Limiting Toxicities (DLTs) of PF-05082566 as single agent and in combination with rituximab [ Time Frame: First 2 cycles of treatment ]

Current Secondary Outcome Measures (submitted: March 4, 2020)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A [ Time Frame: 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 [ Time Frame: 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 Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A [ Time Frame: 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 [ Time Frame: 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.
• Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A [ Time Frame: 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 Maximum Observed Serum Concentration (Cmax) in Portion A [ Time Frame: 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 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A [ Time Frame: Day 1 pre-dose of Cycle 2 ]
  Ctrough of PF-05082566 was observed directly from data.
• PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A [ Time Frame: 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 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A [ Time Frame: 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.
• PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A [ Time Frame: 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.
• PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A [ Time Frame: 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.
• PF-05082566 Clearance (CL) in Portion A [ Time Frame: 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).
• PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A [ Time Frame: 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 [ Time Frame: Up to approximately 2 years ]
  ADA for PF-05082566 was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer>=6.23.
• Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A [ Time Frame: 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.
• Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A [ Time Frame: 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.
• Duration of Response in Portion A [ Time Frame: 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 [ Time Frame: 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.
• Progression-Free Survival in Portion A [ Time Frame: 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.
• Overall Survival in Portion A [ Time Frame: 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 Treatment-Emergent AEs and SAEs in Portion B [ Time Frame: 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.
• Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B [ Time Frame: 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 Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B [ Time Frame: 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 B [ Time Frame: 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.
• Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B [ Time Frame: 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 Cmax in Portion B [ Time Frame: 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 Ctrough in Portion B [ Time Frame: Day 1 pre-dose of Cycle 2 ]
  Ctrough of PF-05082566 was observed directly from data.
• PF-05082566 Tmax in Portion B [ Time Frame: 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 AUClast in Portion B [ Time Frame: 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 AUCinf in Portion B [ Time Frame: 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.
• PF-05082566 AUCtau in Portion B [ Time Frame: 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 [ Time Frame: 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.
• PF-05082566 Vss in Portion B [ Time Frame: 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.
• Rituximab Cmax and Ctrough in Portion B [ Time Frame: Day 1 pre-dose of Cycle 2 ]
  Cmax and Ctrough of rituximab were observed directly from data.
• Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B [ Time Frame: 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.
• Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B [ Time Frame: 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 [ Time Frame: 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 B [ Time Frame: 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.
• Time to Response in Portion B [ Time Frame: 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.
• Progression-Free Survival in Portion B [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: February 28, 2011)

• Adverse events, laboratory abnormalities [ Time Frame: Throughout Study ]
• Pharmacokinetics, Pharmacodynamics, Biomarkers [ Time Frame: Throughout Study ]
• Anti-Drug Antibody levels [ Time Frame: Throughout Study ]
• QTc interval [ Time Frame: Throughout Study ]
• Efficacy [ Time Frame: Throughout Study ]

Current Other Pre-specified Outcome Measures (submitted: March 4, 2020)

• Biomarkers Linked With Immunomodulation and Cytokine Release [ Time Frame: Days 1, 14, 29 and 57 ]
  This was an exploratory endpoint and no data were collected.
• Exploratory Pharmacodynamic Biomarkers [ Time Frame: Days 1 and 21 ]
  This was an exploratory endpoint and no data were collected.
• Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants [ Time Frame: Up to 2 years ]
  This was an exploratory endpoint and was not evaluated. Patient-reported outcome questionnaires were not completed as a result of administrative processing error.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
• Official Title: A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lymphoma, Non-Hodgkin
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Carcinoma, Squamous Cell of Head and Neck
• Malignant Melanoma

Intervention

• Drug: PF-05082566
  Intravenous, Dose escalation, once per month
• Drug: rituximab
  Intravenous, 375 mg/m2, once per week for 4 weeks
  Other Name: Rituxan, MabThera
• Drug: PF-05082566
  IV, Dose escalation, once per month

Study Arms

• Experimental: Portion A
  PF-05082566 single agent in patients with advanced cancer
  Intervention: Drug: PF-05082566
• Experimental: Portion B
  PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
  Interventions:

  • Drug: rituximab
  • Drug: PF-05082566

• Publications *: Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, Cesari R, Chen Y, Davis CB, Huang B, Thall AD, Gopal AK. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018 Apr 15;24(8):1816-1823. doi: 10.1158/1078-0432.CCR-17-1922. Epub 2018 Mar 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 23, 2019): 190
• Original Estimated Enrollment (submitted: February 28, 2011): 78
• Actual Study Completion Date: February 20, 2019
• Actual Primary Completion Date: February 20, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
• Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
• Measurable disease with at least one extranodal tumor mass >1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes >1.5 cm in the GTD.
• ECOG performance status of ≤ 1.
• Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin >9.0 g/dL. For Portion B: ANC ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L, and hemoglobin ≥ 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
• Serum creatinine ≤ 2 x ULN or estimated creatinine clearance ≥ 50 ml/min.
• Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT ≤ 2.5 x ULN.

Exclusion Criteria

• Patients with known symptomatic brain metastases requiring steroids.
• Prior allogeneic hematopoietic stem cell transplant.
• Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
• Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
• Autoimmune disorders and other diseases that compromise or impair the immune system.
• Unstable or serious concurrent medical conditions in the previous 6 months.
• Prior therapy with any anti CD137 monoclonal antibody.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Italy, Japan, United States

Administrative Information

• NCT Number: NCT01307267
• Other Study ID Numbers: B1641001; 2011-002799-17 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2020