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

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 B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available, including SLL/CLL with nodal disease (not including SLL/CLL with >10,000 lymphocytes/μL, prolymphocytic leukemia, hairy cell leukemia, heavy chain disease, plasma cell myeloma, solitary plasmacytoma of bone, extraosseous plasmacytoma, lymphomatoid granulomatosis, and large B cell lymphoma arising in Castleman disease). Additionally, patients enrolled in the MTD expansion cohort must have tumor accessible for repeat biopsy (core needle biopsy preferred).
• Age 18 years or older. Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to 1.
• Adequate bone marrow function, for Portion A defined as absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1,500/μL), platelet count ≥100 x 109/L (≥100,000/μL), and hemoglobin >9.0 g/dL (>5.6 mmol/L), and for Portion B as ANC ≥1.0 x 109/L (≥1,000/uL), platelet count ≥75 x 109/L (≥75000/μL), and hemoglobin >9.0 g/dL (>5.6 mmol/L). In both cases, patients must be transfusion independent (ie, no blood product transfusions for a period of at least 14 days prior to screening).
• Adequate Renal Function, including serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥60 ml/min as calculated using the method standard for the institution.
• Adequate Liver Function, including: a) Total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome; b) Aspartate and Alanine Aminotransferase (AST and ALT) ≤2.0 x ULN; c) Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN in case of bone metastasis).
• Adequate Cardiac Function, as measured by left ventricular ejection fraction (LVEF) that is greater than 40%, or the presence of New York Heart Association (NYHA) classification of no greater than stage II congestive heart failure.

Exclusion Criteria:

• Therapeutic or experimental monoclonal antibodies in last 60 days prior to first dose of study drug.
• Prior therapy with a compound of the same mechanism (interacting with 4-1BB)
• Chemotherapy, cancer immunosuppressive therapy, growth factors, systemic steroids, or investigational agents within 28 days before the first dose of study treatment (for the purposes of this protocol, study treatment includes rituximab in Portion B).
• Prior allogeneic hematopoietic stem cell transplant.
• Central nervous system (CNS) primary or CNS metastatic malignancies.