Biothera has initiated a phase-II clinical trial in stage IV KRAS-mutated colorectal cancer patients with its investigational drug Imprime PGG in combination with Erbitux (cetuximab), the company announced.

Published research demonstrates that colorectal cancers with mutated KRAS genes do not respond to anti-EGFR monoclonal antibodies such as Erbitux. However, researchers believe that Imprime PGG uses the body's own immune system by engaging a type of white blood cell called the neutrophil to fight cancer cells that are coated with antibodies like Erbitux. Such a strategy might be effective against tumours regardless of whether KRAS is mutated or not. Preclinical studies indicate that Imprime PGG in combination with Erbitux can reduce tumour growth.

"About 35-40 percent of all colorectal cancers have a mutation in the KRAS gene," said Leonard B Saltz, medical oncologist and colorectal cancer expert at Memorial Sloan-Kettering Cancer Center, and principal investigator of the trial. "Erbitux and related antibodies are ineffective against these KRAS-mutated cells."

While Erbitux doesn't kill cancer cells that have mutated KRAS, it can bind to the tumour cells and activate the binding of another protein in the immune system called complement to the tumour cell. When neutrophils primed with Imprime PGG bind to the 'fixed' complement on the tumour cell, the neutrophils attack the cancer cell. Imprime PGG is being developed as combination treatment for a wide range of cancers, including colorectal and lung cancer.

"The beauty of this trial design is that since drugs like Erbitux alone can't work in a KRAS-mutated tumour, if we see patients' tumours shrinking, we'll be pretty confident that it is the presence of the investigational drug that is making that happen," said Saltz.

The open-label, 56-patient KRAS-mutated colorectal cancer study is being conducted at three US locations. Patient enrolment begins this week. All subjects will receive Imprime PGG at 4 mg/kg weekly plus standard doses of Erbitux. Tumour measurements and determination of tumour responses for this study will be performed according to Response Evaluation Criteria in Solid Tumours (RECIST).

"Based on the results of our first clinical trial in second- and third-line metastatic colorectal cancer patients, we are excited at the prospect that Imprime PGG in combination with monoclonal anti-EGFR therapies might provide hope to patients with KRAS-mutated tumours," said Daniel K Conners, Biothera chairman and Pharmaceutical Group president. "This KRAS-mutated colorectal trial has the potential to become a pivotal trial and may lead to a fast-track application to the FDA."

Imprime PGGis a novel immunotherapy that works synergistically with anti-tumour monoclonal antibodies to activate a large population of the body's immune cells (neutrophils) to kill cancer cells.

Biothera is a biotechnology company dedicated to improving immune health. The company is developing pharmaceuticals that engage the innate immune system to fight cancer.