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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
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
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
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
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
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
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
Timepoint [5] 0 0
Up to approximately 2 years
Secondary outcome [6] 0 0
PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Timepoint [25] 0 0
Up to approximately 2 years
Secondary outcome [26] 0 0
PF-05082566 Cmax in Portion B
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
Timepoint [27] 0 0
Day 1 pre-dose of Cycle 2
Secondary outcome [28] 0 0
PF-05082566 Tmax in Portion B
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Sex
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
21/06/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/02/2019
Sample size
Target
Accrual to date
Final
190
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/ct2/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