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

Primary Purpose

Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

PF-05082566

rituximab

PF-05082566

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Phase 1, Non-Hodgkin's Lymphoma, Advanced malignancies

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

City of Hope
UC San Diego Moores Cancer Center-Investigational Drug Services
UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
UC San Diego Moores Cancer Center
Research Administration Office: Clinical Research Unit
Ronald Reagan UCLA Medical Center, Drug Information Center
UCLA Bowyer Clinic
UCLA Hematology-Oncology Clinic
Stanford University Medical Center
Stanford University Medical Center
UC San Diego Medical Center - Hillcrest
Santa Monica UCLA Hematology & Oncology Clinic
Stanford University Medical Center
Georgetown University Medical Center Department of Pharmacy, Research
MedStar Georgetown University Hospital
Emory University Hospital Midtown
Emory University Hospital
The Emory Clinic, Building A
The Emory Clinic
Winship Cancer Institute
Brigham and Woman's Hospital
Dana-Farber Cancer Institute
University of Michigan Health System
Siteman Cancer Center-West County
Barnes-Jewish Hospital
Barnes-Jewish Hospital
Washington University Infusion Center Pharmacy
Washington University School of Medicine
Siteman Cancer Center- South County
Siteman Cancer Center - St. Peters
Memorial Sloan Kettering Cancer Center
The University of Texas - M.D. Anderson Cancer Center
South Texas Accelerated Research Therapeutics, LLC
Seattle Cancer Care Alliance
University of Washington Medical Center
Peter MacCallum Cancer Centre
Centre d'investigation clinique
Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
Ospedale San Raffaele di Milano
National Cancer Center Hospital East
Akita University Hospital
The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Portion A

Portion B

Arm Description

PF-05082566 single agent in patients with advanced cancer

PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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).

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.

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.

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.

PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A

Cmax of PF-05082566 was observed directly from data.

PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A

Ctrough of PF-05082566 was observed directly from data.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

Number of Participants With Treatment-Emergent AEs and SAEs in Portion B

Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B

Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B

Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B

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.

PF-05082566 Cmax in Portion B

Cmax of PF-05082566 was observed directly from data.

PF-05082566 Ctrough in Portion B

Ctrough of PF-05082566 was observed directly from data.

PF-05082566 Tmax in Portion B

Tmax of PF-05082566 was observed directly from data as time of Cmax.

PF-05082566 AUClast in Portion B

AUClast of PF-05082566 was determined by linear/log trapezoidal method.

PF-05082566 AUCinf in Portion B

PF-05082566 AUCtau in Portion B

AUCtau of PF-05082566 was determined using linear/log trapezoidal method.

PF-05082566 CL in Portion B

CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.

PF-05082566 Vss in Portion B

Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.

Rituximab Cmax and Ctrough in Portion B

Cmax and Ctrough of rituximab were observed directly from data.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01307267

First Posted

February 28, 2011

Last Updated

March 4, 2020

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01307267

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

June 21, 2011 (Actual)

Primary Completion Date

February 20, 2019 (Actual)

Study Completion Date

February 20, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Phase 1, Non-Hodgkin's Lymphoma, Advanced malignancies

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

190 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Portion A

Arm Type

Experimental

Arm Description

PF-05082566 single agent in patients with advanced cancer

Arm Title

Portion B

Arm Type

Experimental

Arm Description

PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma

Intervention Type

Drug

Intervention Name(s)

PF-05082566

Intervention Description

Intravenous, Dose escalation, once per month

Intervention Type

Drug

Intervention Name(s)

rituximab

Other Intervention Name(s)

Rituxan, MabThera

Intervention Description

Intravenous, 375 mg/m2, once per week for 4 weeks

Intervention Type

Drug

Intervention Name(s)

PF-05082566

Intervention Description

IV, Dose escalation, once per month

Primary Outcome Measure Information:

Title

Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A

Description

Time Frame

Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)

Title

Number of Participants With DLTs in First 2 Cycles of Portion B

Description

Time Frame

Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)

Secondary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A

Description

Time Frame

Up to approximately 2 years

Title

Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A

Description

Time Frame

Up to approximately 2 years

Title

Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A

Description

Time Frame

Up to approximately 2 years

Title

Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A

Description

Time Frame

Up to approximately 2 years

Title

Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A

Description

For vital signs in Portion A, blood pressure and pulse rate were measured. Clinical significance was determined by the investigator.

Time Frame

Up to approximately 2 years

Title

PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A

Description

Cmax of PF-05082566 was observed directly from data.

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

Title

PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A

Description

Ctrough of PF-05082566 was observed directly from data.

Time Frame

Day 1 pre-dose of Cycle 2

Title

PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A

Description

Tmax of PF-05082566 was observed directly from data as time of Cmax.

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.

Title

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

Description

AUClast of PF-05082566 was determined by linear/log trapezoidal method.

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.

Title

PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A

Description

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.

Title

PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A

Description

AUCtau of PF-05082566 was determined using linear/log trapezoidal method.

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.

Title

PF-05082566 Clearance (CL) in Portion A

Description

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).

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.

Title

PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A

Description

Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.

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.

Title

Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A

Description

ADA for PF-05082566 was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer>=6.23.

Time Frame

Up to approximately 2 years

Title

Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A

Description

Time Frame

Up to approximately 2 years

Title

Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A

Description

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)

Title

Duration of Response in Portion A

Description

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)

Title

Time to Response in Portion A

Description

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)

Title

Progression-Free Survival in Portion A

Description

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)

Title

Overall Survival in Portion A

Description

Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.

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)

Title

Number of Participants With Treatment-Emergent AEs and SAEs in Portion B

Description

Time Frame

Up to approximately 4 years

Title

Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B

Description

Time Frame

Up to approximately 4 years

Title

Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B

Description

Time Frame

Up to approximately 2 years

Title

Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B

Description

Time Frame

Up to approximately 2 years

Title

Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B

Description

For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured. Clinical significance was determined by the investigator.

Time Frame

Up to approximately 2 years

Title

PF-05082566 Cmax in Portion B

Description

Cmax of PF-05082566 was observed directly from data.

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.

Title

PF-05082566 Ctrough in Portion B

Description

Ctrough of PF-05082566 was observed directly from data.

Time Frame

Day 1 pre-dose of Cycle 2

Title

PF-05082566 Tmax in Portion B

Description

Tmax of PF-05082566 was observed directly from data as time of Cmax.

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.

Title

PF-05082566 AUClast in Portion B

Description

AUClast of PF-05082566 was determined by linear/log trapezoidal method.

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.

Title

PF-05082566 AUCinf in Portion B

Description

Time Frame

Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.

Title

PF-05082566 AUCtau in Portion B

Description

AUCtau of PF-05082566 was determined using linear/log trapezoidal method.

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.

Title

PF-05082566 CL in Portion B

Description

CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.

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.

Title

PF-05082566 Vss in Portion B

Description

Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.

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.

Title

Rituximab Cmax and Ctrough in Portion B

Description

Cmax and Ctrough of rituximab were observed directly from data.

Time Frame

Day 1 pre-dose of Cycle 2

Title

Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B

Description

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.

Time Frame

Up to approximately 2 years

Title

Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B

Description

Time Frame

Up to approximately 2 years

Title

Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B

Description

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)

Title

Duration of Response in Portion B

Description

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)

Title

Time to Response in Portion B

Description

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)

Title

Progression-Free Survival in Portion B

Description

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)

Title

Overall Survival in Portion B

Description

Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.

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)

Other Pre-specified Outcome Measures:

Title

Biomarkers Linked With Immunomodulation and Cytokine Release

Description

This was an exploratory endpoint and no data were collected.

Time Frame

Days 1, 14, 29 and 57

Title

Exploratory Pharmacodynamic Biomarkers

Description

This was an exploratory endpoint and no data were collected.

Time Frame

Days 1 and 21

Title

Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants

Description

This was an exploratory endpoint and was not evaluated. Patient-reported outcome questionnaires were not completed as a result of administrative processing error.

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

City of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

UC San Diego Moores Cancer Center-Investigational Drug Services

City

La Jolla

State/Province

California

ZIP/Postal Code

92037-0845

Country

United States

Facility Name

UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

UC San Diego Moores Cancer Center

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

Research Administration Office: Clinical Research Unit

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Ronald Reagan UCLA Medical Center, Drug Information Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

UCLA Bowyer Clinic

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

UCLA Hematology-Oncology Clinic

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Stanford University Medical Center

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Facility Name

Stanford University Medical Center

City

Palo Alto

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

UC San Diego Medical Center - Hillcrest

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

Santa Monica UCLA Hematology & Oncology Clinic

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Stanford University Medical Center

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

Georgetown University Medical Center Department of Pharmacy, Research

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

MedStar Georgetown University Hospital

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

Emory University Hospital Midtown

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30308

Country

United States

Facility Name

Emory University Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

The Emory Clinic, Building A

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

The Emory Clinic

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Winship Cancer Institute

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Brigham and Woman's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

University of Michigan Health System

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Siteman Cancer Center-West County

City

Creve Coeur

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Facility Name

Barnes-Jewish Hospital

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110-1094

Country

United States

Facility Name

Barnes-Jewish Hospital

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Washington University Infusion Center Pharmacy

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Siteman Cancer Center- South County

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63129

Country

United States

Facility Name

Siteman Cancer Center - St. Peters

City

Saint Peters

State/Province

Missouri

ZIP/Postal Code

63376

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

The University of Texas - M.D. Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

South Texas Accelerated Research Therapeutics, LLC

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Seattle Cancer Care Alliance

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Facility Name

University of Washington Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98195

Country

United States

Facility Name

Peter MacCallum Cancer Centre

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3000

Country

Australia

Facility Name

Centre d'investigation clinique

City

RENNES cedex 9

ZIP/Postal Code

35033

Country

France

Facility Name

Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi

City

Bologna

State/Province

ZIP/Postal Code

40138

Country

Italy

Facility Name

Ospedale San Raffaele di Milano

City

Milano

State/Province

ZIP/Postal Code

20132

Country

Italy

Facility Name

National Cancer Center Hospital East

City

Kashiwa

State/Province

Chiba

ZIP/Postal Code

277-8577

Country

Japan

Facility Name

Akita University Hospital

City

Akita

ZIP/Postal Code

010-8543

Country

Japan

Facility Name

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

City

Tokyo

ZIP/Postal Code

135-8550

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing 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.

Citations:

PubMed Identifier

32144134

Citation

Gopal AK, Levy R, Houot R, Patel SP, Popplewell L, Jacobson C, Mu XJ, Deng S, Ching KA, Chen Y, Davis CB, Huang B, Fly KD, Thall A, Woolfson A, Bartlett NL. First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973. Epub 2020 Mar 6.

Results Reference

derived

PubMed Identifier

29549159

Citation

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.

Results Reference

derived

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1641001&StudyName=A%20Study%20Of%20PF-05082566%20As%20A%20Single%20Agent%20And%20In%20Combination%20With%20Rituximab

Description

To obtain contact information for a study center near you, click here.

Learn more about this trial

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

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