Clinical trial NCT01307267: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-03-02
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
timeFrame: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
measure: Number of Participants With DLTs in First 2 Cycles of Portion B
timeFrame: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
timeFrame: Up to approximately 2 years
measure: Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
timeFrame: Up to approximately 2 years
measure: Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
timeFrame: Up to approximately 2 years
measure: Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
timeFrame: Up to approximately 2 years
measure: Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
timeFrame: Up to approximately 2 years
measure: PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
timeFrame: 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
measure: PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A
timeFrame: Day 1 pre-dose of Cycle 2
measure: PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A
timeFrame: 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.
measure: PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A
timeFrame: 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.
measure: PF-05082566 Clearance (CL) in Portion A
timeFrame: 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.
measure: PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A
timeFrame: 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.
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A
timeFrame: Up to approximately 2 years
measure: Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A
timeFrame: Up to approximately 2 years
measure: Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A
timeFrame: 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)
measure: Duration of Response in Portion A
timeFrame: 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)
measure: Time to Response in Portion A
timeFrame: 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)
measure: Progression-Free Survival in Portion A
timeFrame: 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)
measure: Overall Survival in Portion A
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent AEs and SAEs in Portion B
timeFrame: Up to approximately 4 years
measure: Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B
timeFrame: Up to approximately 4 years
measure: Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
timeFrame: Up to approximately 2 years
measure: Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
timeFrame: Up to approximately 2 years
measure: Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B
timeFrame: Up to approximately 2 years
measure: PF-05082566 Cmax in Portion B
timeFrame: 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.
measure: PF-05082566 Ctrough in Portion B
timeFrame: Day 1 pre-dose of Cycle 2
measure: PF-05082566 Tmax in Portion B
timeFrame: 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.
measure: PF-05082566 AUClast in Portion B
timeFrame: 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.
measure: PF-05082566 AUCinf in Portion B
timeFrame: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
measure: PF-05082566 AUCtau in Portion B
timeFrame: 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.
measure: PF-05082566 CL in Portion B
timeFrame: 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.
measure: PF-05082566 Vss in Portion B
timeFrame: 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.
measure: Rituximab Cmax and Ctrough in Portion B
timeFrame: Day 1 pre-dose of Cycle 2
measure: Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B
timeFrame: Up to approximately 2 years
measure: Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B
timeFrame: Up to approximately 2 years
measure: Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B
timeFrame: 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)
measure: Duration of Response in Portion B
timeFrame: 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)
measure: Time to Response in Portion B
timeFrame: 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)
measure: Progression-Free Survival in Portion B
timeFrame: 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)
measure: Overall Survival in Portion B
timeFrame: 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 outcomes:
measure: Biomarkers Linked With Immunomodulation and Cytokine Release
timeFrame: Days 1, 14, 29 and 57
measure: Exploratory Pharmacodynamic Biomarkers
timeFrame: Days 1 and 21
measure: Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants
timeFrame: Up to 2 years
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center-Investigational Drug Services
state: California
city: La Jolla
country: United States
facility: UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Research Administration Office: Clinical Research Unit
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center, Drug Information Center
state: California
city: Los Angeles
country: United States
facility: UCLA Bowyer Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology-Oncology Clinic
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: Santa Monica
country: United States
facility: Santa Monica UCLA Hematology & Oncology Clinic
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center Department of Pharmacy, Research
state: District of Columbia
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic, Building A
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Brigham and Woman's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Creve Coeur
country: United States
facility: Siteman Cancer Center-West County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Infusion Center Pharmacy
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center- South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St. Peters
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: The University of Texas - M.D. Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: RENNES cedex 9
country: France
facility: Centre d'investigation clinique
city: Bologna
country: Italy
facility: Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
state: BO
city: Milano
country: Italy
facility: Ospedale San Raffaele di Milano
state: MI
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Akita
country: Japan
facility: Akita University Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.
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.