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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Carcinoma, Renal Cell; Malignant Melanoma; Lymphoma, Follicular; Carcinoma, Non-Small-Cell Lung; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Carcinoma, Squamous Cell of Head and Neck

Treatments: Drug: rituximab; Drug: PF-05082566

Study type: Interventional

Funder types: Industry

Identifiers

NCT01307267

2011-002799-17 (EudraCT Number)

B1641001

Details and patient eligibility

About

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).

Enrollment: 190 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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190 participants in 2 patient groups

Portion A

Experimental group

Description:

PF-05082566 single agent in patients with advanced cancer

Treatment:

Drug: PF-05082566

Drug: PF-05082566

Portion B

Experimental group

Description:

PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma

Treatment:

Drug: PF-05082566

Drug: rituximab

Drug: PF-05082566