With the support of CIRM DT (DR1-01485) we developed Hu5F9-G4, a humanized monoclonal CD47-blocking antibody as a novel immunotherapy for patients with hematological malignancies and solid tumors. CD47 is an anti-phagocytic “don’t eat me” signal that is expressed at relatively high levels on most human cancers. Inhibition of CD47-SIRPalpha signaling enables anti-tumor targeting through the innate and adaptive immune system in a broad range of preclinical in vivo models.
The goal of CIRM DTIII Grant (DR3-06965) is to conduct phase I clinical trials to determine safety and establish the dose for subsequent trials that will explore the efficacy of the novel antibody. Hu5F9-G4 is currently being explored in two phase 1 trials; one for patients with solid tumors at Stanford University that started in August 2014 (NCT02216409) and a multi-center study for patients with acute myelogenous leukemia (AML) in the United Kingdom (NCT02678338) that started in December 2015. The primary objectives for both trials are to assess safety and tolerability, secondary objectives are to assess pharmaco-kinetics (PK) and pharmaco–dynamics (PD).
The solid tumor trial consists of two parts, Part A to determine the optimal first “Priming” dose, and Part B to determine the optimal “Maintenance” dose. The priming dose has been identified and the trial has progressed from Part A to part B to determine to the optimal maintenance dose. No dose limiting toxicities have occurred in Part B and the study continues dosing as planned an according to the milestones.
The AML trial has administered Hu5F9-G4 to the patients in the first two dosing cohorts. The infusions have been well tolerated and the trial is progressing according to the study design and the milestones of the grant.
In summary, during the last year, the Hu5F9-G4 clinical trials have made substantial progress and milestones have been met.