Phase 1 Clinical Trial of KB004 in EphA3-Expressing Hematologic Malignancies Expanded with Treatment of First Patient in Australian Site
Monash cancer research leads to new investigational cancer drug
Cancer research by a team of scientists lead by Monash University's A/Prof. Martin Lackmann, on a potential new anti-cancer target, EphA3, has resulted in an investigational therapeutic in a Phase 1 clinical trial at the Alfred Hospital in Melbourne. The study is being conducted in patient populations with hematologic malignancies, including acute myelogenous leukaemia, chronic myelogenous leukaemia, acute lymphocytic leukaemia, and myelodysplastic syndromes.
Dr. Andrew Wei led a clinical team at the Alfred Hospital, which treated the first patient in Australia with the new investigational therapeutic called KB004, a monoclonal antibody that is designed to destroy leukemic cells, leukemic stem cells, as well as the newly forming tumour vasculature. The trial at the Alfred Hospital is part of a multi-centre open-label Phase 1 trial organised and sponsored by KaloBios Pharmaceuticals, a U.S.-based privately held Biotechnology Company who has supported research in Dr. Lackmann's team since 2006.
Realising its potential as a target for anti-cancer therapy, the Lackmann laboratory, together with a team of Australian collaborators including Professors Andrew Boyd from the Queensland Institute of Medical Research, who discovered EphA3, and Andrew Scott from the Ludwig Institute for Cancer Research, developed an early version of the anti-EphA3 antibody as potential anti-cancer agent.
"We are very excited to see progression of KB004 into the clinic, and in particular to be part of the multi-centre trial that allows us to treat leukaemia patients at the Alfred Hospital with the new investigational therapy" said A/Prof Lackmann when the trial opened in Melbourne earlier this month.
Dr. Andrew Wei said this Phase I trial is designed to assess the safety and tolerability of KB004 at doses up to 700 mg in patients with leukaemia and observe if there potentially is a positive effect of the treatment on disease outcome. "The target of KB004 seems to be present almost exclusively on cancer cells and the preclinical safety data for this therapeutic along with the safety data from the first trial patients in U.S. centres have been encouraging. We are enthusiastic that this trial may help translate the exciting preclinical activity findings successfully into a potential new therapy for patients with leukaemia."
KB004 was engineered by a team of scientists at KaloBios Pharmaceuticals in San Francisco, who used proprietary antibody HumaneeringTM technology and the blueprint of the original monoclonal antibody to develop the recombinant human version with enhanced therapeutic functions. The high similarity of KB004's primary structure with human antibody germ-line sequences may result in low immunogenicity in patients even after prolonged treatments.
According to Dr. Geoffrey Yarranton, Chief Scientific Officer at KaloBios, the specificity of the antibody for cancer cells, combined with potential low immunogenicity are some of KB004's great attributes. "Our experience to date suggests that KB004 may only target leukemic, but not healthy white blood cells, a property that differentiates it from many other cancer drugs," Dr. Yarranton said.
While the current trial, which already started patient recruitment at two US Cancer Centres in 2010, is recruiting only leukaemia patients, the target protein EphA3 is also present in solid tumours. "We believe this antibody could provide significant benefit to patients with a broad range of cancer types, given its potential to affect tumour growth through several distinct mechanisms," said A/Prof Lackmann.