A breakthrough trial targeting Glioblastoma, one of the most aggressive and deadly forms of brain cancer, is giving hope to patients and their families after successful initial clinical results.
Brain cancer, in particular Glioblastoma, is one of the most challenging forms of cancer to cure. There are limited options for treatment and for most, it’s deadly.
An ONJCRI-sponsored trial funded by the Cure Brain Cancer Foundation, and with study drug provided by Humanigen, is hoping to change that, by targeting the microenvironment within brain cancer with a new humanised antibody called ifabotuzumab (formerly KB004). Head of the ONJCRI Tumour Targeting Program, and lead molecular imaging and scientific investigator, Professor Andrew Scott said that the phase 1 trial, completed in 2021, was a world first and has shown some highly promising results.
“The trial itself explored the safety and bioimaging of using ifabotuzumab in patients diagnosed with Glioblastoma,” said Professor Scott. “This antibody has been evaluated in patients with blood cancer in the past, but it has never been evaluated in patients with solid tumours and certainly not brain cancer. Ifabotuzumab is unusual because by targeting the EphA3 receptor, it doesn’t just attach to cancer cells, it also attaches to the microenvironment that exists within the cancer.”
The team set out to develop an innovative imaging approach where they tagged ifabotuzumab with a radioactive positron emitting tracer. This allowed the team to image where the antibody moved throughout the body using positron emission tomography (PET) and demonstrated that ifabotuzumab selectively targeted the sites of the tumour in the brain.
“We were very excited because not only were we able to demonstrate ifabotuzumab’s safety, but the results were even better than we anticipated. By tracing ifabotuzumab in this way, we were able to observe that high concentrations of the drug went directly into the site of the tumour without inadvertently binding to healthy tissue. To our delight, images of every single patient in the trial showed the tumours lighting up, which is significant.”
Professor Hui Gan, Clinician-Scientist, and Co-Director of the Centre for Research Excellence in Brain Cancer at the ONJCRI was the oncology lead for the trial and was equally impressed.
“Glioblastoma is a very aggressive form of brain cancer, with no treatment shown to prolong survival at the time of inevitable relapse. These results are very encouraging, and Ifabotuzumab should further be developed as a new treatment for patients.”
This project has been a great example of translational research and highlights the crucial need for collaboration between laboratory researchers and clinicians to gain the best possible outcome for cancer patients.
“Not only did the collaboration between scientists and clinicians directly lead to the rapid translation of ifabotuzumab into the clinic, the on-going collaboration has allowed myself and my clinical team to feed our observations back to the laboratory and this is helping us develop the next generation of these drugs.”
While the trial was a joint effort between both Professor Gan and Professor Scott, many people have been involved in the process.
“It really has been a team effort,” says Professor Scott, “Professor Peter Janes, Head of the Receptor Biology Laboratory, Dr Jodie Palmer, Clinical Projects Manager, and Drs Christian Wichmann and Ingrid Burvenich along with the rest of the Tumour Targeting Laboratory have all been instrumental in getting to this point.”
This project has really come full circle for Professor Scott, who was central to the original development of ifabotuzumab.
“An interesting part of the story is that the development of the antibody originally came from a collaboration established between myself and two collaborators Professor Andrew Boyd (WEHI and QIMR) and Professor Martin Lackmann (Monash University) some 15 years ago, and after extensive research the antibody was licensed to the US biotech company, Humanigen, and has been developed into the drug ifabotuzumab.”
“To see something that you spent a long time developing, tested in this way is very gratifying, but to then to see the results in the first patient and achieve results better than I was hoping for is a very proud moment. It’s been a great journey, but it’s also just part of the journey. We now need to try and take it to the next level.”
On the back of the trial’s success, the ONJCRI and Humanigen are now working together on developing an ifabotuzumab-based antibody drug conjugate that they will then take into a first in human clinical trial by the end of 2023.
“After the initial trial, we and Humanigen decided that ifabotuzumab is an ideal candidate to deliver cancer killing drug payloads to cancers, including brain cancer but also other cancers such as lung cancer, colon cancer and breast cancer. The next phase of clinical trials will include a range of patients with these conditions, so we really hope that these drugs will become an effective treatment for patients with a range of devastating cancer diagnoses.”