A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
Condition: 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
MeSH terms: Lymphoma; Carcinoma; Melanoma; Carcinoma, Non-Small-Cell Lung; Lymphoma, Non-Hodgkin; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Squamous Cell Carcinoma of Head and Neck
Intervention: PF-05082566; rituximab; PF-05082566
Intervention description: Intravenous, Dose escalation, once per month; Intravenous, 375 mg/m2, once per week for 4 weeks; IV, Dose escalation, once per month
Intervention MeSH terms: Rituximab; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 190.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase 1; Non-Hodgkin's Lymphoma; Advanced malignancies

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.