A Study of PF-05082566 In Combination With Mogamulizumab In Patients With Advanced Solid Tumors

A PHASE 1B STUDY OF PF-05082566 IN COMBINATION WITH MOGAMULIZUMAB (KW-0761) IN PATIENTS WITH ADVANCED SOLID TUMORS

This study is a Phase 1b, open label, multi center, multi-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended dose for phase 2 (RP2D) investigations of PF- 05082566 in combination with KW-0761 (mogamulizumab) in patients with advanced solid tumors. Once the MTD of PF-05082566 administered in combination with KW-0761 is estimated (dose finding), one or more expansion cohorts of patients with selected advanced solid tumors (dose-expansion ) will be enrolled to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarkers modulation.

Inclusion Criteria:

• Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy. Dose Finding Cohorts: Tumor types will be limited to CRC, SCCHN, squamous NSCLC, bladder, or ovarian carcinomas which have progressed on standard therapy, or for which no standard therapy is available.
• Measurable disease by RECIST version 1.1.
• For Expansion Cohorts only: patients must have tumor accessible for biopsies (core needle biopsy or excision preferred).
• Age 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow, renal and liver function.
• Serum/urine pregnancy test (for females of childbearing potential) negative at screening and before the patient will receive the study treatment.
• Male and female patients of childbearing potential and at risk for pregnancy must agree to use two (2) highly effective methods of contraception throughout the study and for 60 days after the last dose of assigned study treatment.

Exclusion Criteria:

• Active central nervous system primary or secondary malignancies, active seizure disorder, spinal cord compression, or carcinomatous meningitis.
• Therapeutic or experimental monoclonal antibodies in last 60 days prior registration.
• Systemic anticancer therapy or major surgery within 28 days prior to registration. In absence of toxicity from prior systemic anticancer therapy, 5 half-lives since completion of prior systemic anticancer therapy is allowed.
• Systemic steroids, any other form of immunosuppressive therapy or radiation therapy within 14 days prior to registration.
• Live vaccine within 30 days prior to registration.
• Severe hypersensitivity reaction to treatment with another monoclonal antibody, known or suspected hypersensitivity to study drugs or any component of their formulation.
• History of autoimmune disease or known inflammatory bowel disease.
• Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy) or any of the following within 12 months prior to registration: myocardial infarction, congenital long QT syndrome, torsade de points, arrhythmias, right bundle branch block and left anterior hemiblock uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, ongoing NCICTCAE Grade 2 cardiac dysrhythmias, atrial fibrillation or QTcF interval >470 msec.