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PROTOCOL FULL TITLE A phase 1, Open-Label, Dose Escalation Study of PF-04518600 as a single agent and in combination with PF-05082566 in Patients with Selected Locally Advanced or Metastatic Carcinomas
Clinical Trial ( IRB ) #: 16-227-3
Title: PROTOCOL FULL TITLE A phase 1, Open-Label, Dose Escalation Study of PF-04518600 as a single agent and in combination with PF-05082566 in Patients with Selected Locally Advanced or Metastatic Carcinomas
Principal Investigator: Dr. Jeffrey wasser
Description: Background: PF-04518600 and PF-05082566 are antibodies (a type of protein) which have been shown to stimulate the immune system. Research has shown that an immune response like this can work against tumor cells to slow tumor growth by causing tumor cells to die. PF-04518600 alone and in combination with PF-05082566 are being investigated as possible treatments for patients with advanced liver, skin (melanoma), kidney, head and neck, stomach, cervical, gastric, bladder or lung cancer. Rationale for this study: The ability to escape immune recognition is a hallmark of cancer progression. By manipulating the immune system and restoring immune surveillance, immunotherapy offers the opportunity to not only eradicate or stop tumor growth, but also the opportunity to decrease the rate of recurrence.1 One strategy for increasing tumor immunity would be to activate and expand tumor-associated antigen T cells. It has long been recognized that T cell activation is not mediated by antigen stimulation alone. Indeed, tumor antigens may induce T-cell anergy, rendering T cells unable to proliferate in response to antigen, and hypo-responsive to further antigen encounter. Instead, co-stimulatory receptors are required to complete the process of T cell activation and expansion. Thus, co-stimulatory receptors may have the potential to prevent tumor-induced immune tolerance. PF-04518600 is a fully human Immunoglobulin G2 (IgG2) agonistic monoclonal antibody that is highly selective for human OX40 (CD134). PF-04518600’s agonistic potential was revealed in a 293 luciferase reporter assay, whereby induced OX40 mediated NFkB activation, and luciferase activity increased dose proportionally to increasing concentrations of PF-04518600. Selectivity studies using a biacore assay also revealed PF-04518600 to be highly selective for OX40, with no cross activity with other members of the TNFR super-family, including CD40 receptor, 4-1BB receptor (CD137) and glucocorticoid-induced TNFR family related gene (GITR). Study Design: This is a Phase 1, open label unblinded manner, multi-center, multiple dose, dose escalation, safety,pharmacokinetic, and pharmacodynamic study of PF-04518600 monotherapy (Part A) and PF-04518600 plus PF-05082566 combination therapy (Part B). Both Part A and Part B will be further divided into a dose escalation phase, and a dose expansion phase. Study Population and Sample Size: Adults (men and women) age 18 years and over. Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, clear cell RCC urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix. A maximum of approximately 190 patients are expected to be enrolled into the study. Major Study Interventions: For monotherapy, patients will be dosed at 0.01 mg/kg PF-04518600 in the first cohort. For combination therapy, patients will be dosed at 0.1 mg/kg PF-04518600 and 20 mg PF-05082566 in the first dose combination level. Main Outcome measures /Analyses: To assess safety, and tolerability at increasing dose levels of PF-04518600 in patients with selected advanced or metastatic solid tumors in order to establish the MTD. Primary Objectives: -To establish the RP2D of PF-04518600 in patients with selected advanced or metastatic solid tumors. To further characterize the safety and tolerability of PF-04518600 in patients with selected advanced or metastatic solid tumors. Secondary Objectives: -To assess preliminary anti-tumor clinical activity of PF-04518600 in patients with selected advanced or metastatic solid tumors solid tumors. To characterize the single dose and multiple dose PK of PF-04518600 following IV administration. -To characterize the degree of TE by PF-04518600 at multiple doses
Classification:
  Cancer - General
Eligibility Criteria: Check with study contact
How to Contact: Christopher Sampson. Telephone: 860-679-6580. Email: sampson@uchc.edu or Quratulain Ali. Telephone: 860-679-7648. Email: Qali@uchc.edu
Enrollment Status/Comments: Enrolling/recruiting. For current recruitment status, please check with study contact.