US-based Peregrine Pharmaceuticals has initiated an investigator-sponsored trial (IST) of its investigational immunotherapy bavituximab in combination with Bristol-Myers Squibb's ipilimumab (Yervoy), to treat advanced melanoma.
Bavituximab targets phosphatidylserine (PS), a highly immunosuppressive molecule exposed on cells that line tumour blood vessels and tumour cells.
Data from preclinical studies in a model of melanoma show that the combination of a bavituximab equivalent and ipilimumab yield improved anti-tumour activity compared to ipilimumab alone.
The trial is being carried out at the University of Texas Southwestern Medical Center, Dallas, by Arthur Frankel, professor of internal medicine at the Simmons Comprehensive Cancer Center.
The company's lead immuno-oncology candidate bavituximab is currently being evaluated in second-line non-small cell lung cancer (NSCLC), as part of the SUNRISE Phase III clinical trial.
Peregrine vice-president of clinical and regulatory affairs Joseph Shan said: "We are particularly excited as this trial is designed to provide proof-of-concept data for this potentially innovative upstream and downstream checkpoint inhibitor combination.
"In addition, the trial's open-label design allows for the potential for data readouts throughout the course of the trial."
The investigator-sponsored trial is an open label, two-arm, randomised, single-centre Phase Ib trial of bavituximab plus ipilimumab (Yervoy), in patients with advanced melanoma.
In this trial, a total of 24 patients will be randomised into two treatment groups A and B.
In group A, about 16 patients will be enrolled and they will be given two weekly doses of bavituximab (3mg/kg) followed by combination therapy of ipilimumab (up to four cycles at 3mg/kg every three weeks) plus bavituximab (3mg/kg weekly for 12 weeks)
In group B eight patients will be given standard ipilimumab alone (up to four cycles at 3mg/kg every three weeks).
The trial's primary endpoint will be safety, while secondary endpoints include measurements of disease control rate (DCR) and overall survival (OS).
In addition, tumour biopsies will be collected at screening in order to measure changes in myeloid-derived suppressor cells (MDSC), tumour-associated macrophages (TAM), T-regulatory cells (Treg) and peripheral blood cytokines.