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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01307267
First received: February 28, 2011
Last updated: August 2, 2016
Last verified: August 2016
  Purpose
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).

Condition Intervention Phase
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
Drug: PF-05082566
Drug: rituximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: First 2 cycles (56 days) of treatment ] [ Designated as safety issue: Yes ]
    Dose Limiting Toxicities (DLTs) of PF-05082566 as single agent

  • Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: First 2 cycles (56 days) of treatment ] [ Designated as safety issue: Yes ]
    Dose Limiting Toxicities (DLTs) of PF-05082566 in combination with rituximab


Secondary Outcome Measures:
  • Pharmacokinetics (Tmax) of PF-05082566 and rituximab when given in combination [ Time Frame: Days -7, 0, 1, 3, 7, 1, 22, 29, 36, 43, 50, 57, 78, 85, 112 and 141, followed by every 28 days during the therapy up to 2 years. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (Tmax) of PF-05082566 as a single agent [ Time Frame: Days 1, 3, 8, 15, 22, 29, 31, 36, 43, 50, 57, 64, 71, 78, 85, 87, 112, followed by every 28 days during the therapy up to 2 years, then Days 28, 57 and 85 after the administration of the last dose. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Presence of Anti-Drug Antibodies against PF-05082566 (Portion A) [ Time Frame: Days 1, 8, 15, 29, 36, 43, 57, 71, 127, 145 and every 28 days up to 2 years during the treatment and end of treatment ] [ Designated as safety issue: Yes ]
  • Presence of Anti-Drug Antibodies against PF-05082566 and rituximab (Portion B) [ Time Frame: Every 28 days during the treatment up to 2 years and at the end of treatment ] [ Designated as safety issue: Yes ]
  • Analysis of biomarkers linked with immunomodulation/cytokine release [ Time Frame: Days 1, 14, 29 and 57 ] [ Designated as safety issue: Yes ]
  • Analysis of exploratory pharmacodynamic biomarkers [ Time Frame: Days 1 and 21 ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by: Objective Response Rate of PF-05082566 as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Objective Response Rate of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (Cmax) of PF-05082566 and rituximab when given in combination [ Time Frame: Days -7, 0, 1, 3, 7, 1, 22, 29, 36, 43, 50, 57, 78, 85, 112 and 141, followed by every 28 days during the therapy up to 2 years. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (AUC) of PF-05082566 and rituximab when given in combination [ Time Frame: Days -7, 0, 1, 3, 7, 1, 22, 29, 36, 43, 50, 57, 78, 85, 112 and 141, followed by every 28 days during the therapy up to 2 years. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (Cmax) of PF-05082566 as a single agent [ Time Frame: Days 1, 3, 8, 15, 22, 29, 31, 36, 43, 50, 57, 64, 71, 78, 85, 87, 112, followed by every 28 days during the therapy up to 2 years, then Days 28, 57 and 85 after the administration of the last dose. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (AUC) of PF-05082566 as a single agent [ Time Frame: Days 1, 3, 8, 15, 22, 29, 31, 36, 43, 50, 57, 64, 71, 78, 85, 87, 112, followed by every 28 days during the therapy up to 2 years, then Days 28, 57 and 85 after the administration of the last dose. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Efficacy as measured by: Duration of Response of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Progression Free Survival of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Overall Survival of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Duration of Response of PF-05082566 as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Progression Free Survival of PF-05082566 given as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Overall Survival of PF-05082566 given as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 220
Study Start Date: June 2011
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
PF-05082566 single agent in patients with advanced cancer
Drug: PF-05082566
Intravenous, Dose escalation, once per month
Experimental: B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
Drug: rituximab
Intravenous, 375 mg/m2, once per week for 4 weeks
Other Name: Rituxan, MabThera
Drug: PF-05082566
IV, Dose escalation, once per month

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307267

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

  Show 37 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01307267     History of Changes
Other Study ID Numbers: B1641001  2011-002799-17 
Study First Received: February 28, 2011
Last Updated: August 2, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Phase 1
Non-Hodgkin's Lymphoma
Advanced malignancies

Additional relevant MeSH terms:
Lymphoma
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lymphoma, Non-Hodgkin
Carcinoma, Renal Cell
Carcinoma, Squamous Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Head and Neck Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Glandular and Epithelial
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on August 29, 2016