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)
- 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
- 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.
- 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.