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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01307267




Registration number
NCT01307267
Ethics application status
Date submitted
28/02/2011
Date registered
2/03/2011
Date last updated
17/03/2020

Titles & IDs
Public title
A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
Scientific 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)
Secondary ID [1] 0 0
2011-002799-17
Secondary ID [2] 0 0
B1641001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin 0 0
Lymphoma, Follicular 0 0
Lymphoma, Large B-Cell, Diffuse 0 0
Carcinoma, Non-Small-Cell Lung 0 0
Carcinoma, Renal Cell 0 0
Carcinoma, Squamous Cell of Head and Neck 0 0
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-05082566
Treatment: Drugs - rituximab
Treatment: Drugs - PF-05082566

Experimental: Portion A - PF-05082566 single agent in patients with advanced cancer

Experimental: Portion B - PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma


Treatment: Drugs: PF-05082566
Intravenous, Dose escalation, once per month

Treatment: Drugs: rituximab
Intravenous, 375 mg/m2, once per week for 4 weeks

Treatment: Drugs: PF-05082566
IV, Dose escalation, once per month

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A - 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.
Timepoint [1] 0 0
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
Primary outcome [2] 0 0
Number of Participants With DLTs in First 2 Cycles of Portion B - 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.
Timepoint [2] 0 0
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
Secondary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A - 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.
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A - 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).
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A - 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.
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A - 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.
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A - For vital signs in Portion A, blood pressure and pulse rate were measured. Clinical significance was determined by the investigator.
Timepoint [5] 0 0
Up to approximately 2 years
Secondary outcome [6] 0 0
PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A - Cmax of PF-05082566 was observed directly from data.
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A - Ctrough of PF-05082566 was observed directly from data.
Timepoint [7] 0 0
Day 1 pre-dose of Cycle 2
Secondary outcome [8] 0 0
PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A - Tmax of PF-05082566 was observed directly from data as time of Cmax.
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
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 - AUClast of PF-05082566 was determined by linear/log trapezoidal method.
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A - 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.
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A - AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
PF-05082566 Clearance (CL) in Portion A - 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).
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A - Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Timepoint [13] 0 0
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.
Secondary outcome [14] 0 0
Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A - ADA for PF-05082566 was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer>=6.23.
Timepoint [14] 0 0
Up to approximately 2 years
Secondary outcome [15] 0 0
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A - 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.
Timepoint [15] 0 0
Up to approximately 2 years
Secondary outcome [16] 0 0
Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A - 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.
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Duration of Response in Portion A - 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.
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Time to Response in Portion A - 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.
Timepoint [18] 0 0
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)
Secondary outcome [19] 0 0
Progression-Free Survival in Portion A - 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.
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
Overall Survival in Portion A - Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Timepoint [20] 0 0
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)
Secondary outcome [21] 0 0
Number of Participants With Treatment-Emergent AEs and SAEs in Portion B - 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.
Timepoint [21] 0 0
Up to approximately 4 years
Secondary outcome [22] 0 0
Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B - 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).
Timepoint [22] 0 0
Up to approximately 4 years
Secondary outcome [23] 0 0
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B - 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.
Timepoint [23] 0 0
Up to approximately 2 years
Secondary outcome [24] 0 0
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B - 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.
Timepoint [24] 0 0
Up to approximately 2 years
Secondary outcome [25] 0 0
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B - For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured. Clinical significance was determined by the investigator.
Timepoint [25] 0 0
Up to approximately 2 years
Secondary outcome [26] 0 0
PF-05082566 Cmax in Portion B - Cmax of PF-05082566 was observed directly from data.
Timepoint [26] 0 0
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.
Secondary outcome [27] 0 0
PF-05082566 Ctrough in Portion B - Ctrough of PF-05082566 was observed directly from data.
Timepoint [27] 0 0
Day 1 pre-dose of Cycle 2
Secondary outcome [28] 0 0
PF-05082566 Tmax in Portion B - Tmax of PF-05082566 was observed directly from data as time of Cmax.
Timepoint [28] 0 0
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.
Secondary outcome [29] 0 0
PF-05082566 AUClast in Portion B - AUClast of PF-05082566 was determined by linear/log trapezoidal method.
Timepoint [29] 0 0
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.
Secondary outcome [30] 0 0
PF-05082566 AUCinf in Portion B - 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.
Timepoint [30] 0 0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
Secondary outcome [31] 0 0
PF-05082566 AUCtau in Portion B - AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
Timepoint [31] 0 0
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.
Secondary outcome [32] 0 0
PF-05082566 CL in Portion B - CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.
Timepoint [32] 0 0
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.
Secondary outcome [33] 0 0
PF-05082566 Vss in Portion B - Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Timepoint [33] 0 0
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.
Secondary outcome [34] 0 0
Rituximab Cmax and Ctrough in Portion B - Cmax and Ctrough of rituximab were observed directly from data.
Timepoint [34] 0 0
Day 1 pre-dose of Cycle 2
Secondary outcome [35] 0 0
Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B - 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.
Timepoint [35] 0 0
Up to approximately 2 years
Secondary outcome [36] 0 0
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B - 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.
Timepoint [36] 0 0
Up to approximately 2 years
Secondary outcome [37] 0 0
Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B - 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.
Timepoint [37] 0 0
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)
Secondary outcome [38] 0 0
Duration of Response in Portion B - 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.
Timepoint [38] 0 0
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)
Secondary outcome [39] 0 0
Time to Response in Portion B - 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.
Timepoint [39] 0 0
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)
Secondary outcome [40] 0 0
Progression-Free Survival in Portion B - 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.
Timepoint [40] 0 0
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)
Secondary outcome [41] 0 0
Overall Survival in Portion B - Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Timepoint [41] 0 0
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)

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
France
State/province [10] 0 0
RENNES cedex 9
Country [11] 0 0
Italy
State/province [11] 0 0
BO
Country [12] 0 0
Italy
State/province [12] 0 0
MI
Country [13] 0 0
Japan
State/province [13] 0 0
Chiba
Country [14] 0 0
Japan
State/province [14] 0 0
Akita
Country [15] 0 0
Japan
State/province [15] 0 0
Tokyo

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT01307267
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications