Immunotherapy together with an experimental cancer drug could offer a new way of treating some patients with aggressive brain cancers, promising early results from a Phase I trial suggest. Image Paediatric brain tumour cells. Credit: ICR, Valeria Molinari, Louise Howell, Maria Vinci, Katy Taylor, Chris Jones Two of the first 10 patients treated for a highly aggressive type of brain cancer called glioblastoma responded to the immunotherapy agent atezolizumab when combined with ipatasertib, a new precision drug that may be able to uncloak tumours to the immune system. Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust found particular signs of effectiveness in patients with defects in a key gene called PTEN. Two patients who received the combination saw their cancer shrink or stop growing – in fact, one of these patients’ tumour seems to have disappeared completely. It is unusual to see such positive clinical responses in Phase I clinical trials – which are run in patients who have advanced cancer as a way of testing a drug's safety and appropriate dosage. However, these are early results and further research is needed before drawing any conclusions. 10 patients recruited to Ice-CAP trial So far, researchers have recruited 10 patients with glioblastoma who had relapsed after treatment to the Phase I Ice-CAP trial. Seven of them had tumours with defects in the PTEN gene and four patients had complete loss of PTEN expression. The trial, supported by the immunotherapy Centers Of Research Excellence (imCORE) network, a Roche academic-industry partnership, and the NIHR Biomedical Research Centre at The Royal Marsden and the ICR, is still open for recruitment. Initial results presented at the American Association of Cancer Research (AACR) Annual Meeting 2021 show that two out of four patients with complete PTEN loss responded to treatment. The Ice-CAP trial, led by the ICR’s Investigator Initiated Trials team within the Drug Development Unit, is testing the effect of combining the immunotherapy drug atezolizumab with the precision drug ipatasertib, which blocks a molecule called AKT. Growth signals involving AKT are used by cancers that lack a functioning PTEN gene to grow and spread, which explains why patients with PTEN defects might benefit most from the combination. No signs of disease 22 months later One patient of the two patients who responded and had aggressive brain cancer with faulty PTEN genes, responded remarkably well to the drug combination – still showing no signs of disease 22 months later. Previous studies have suggested that defects in the PTEN gene weaken the anti-cancer immune response, reducing the ability of the immune system to kill cancer cells. Ipatasertib seems to be able to turn the anti-cancer immune response back up again, giving it the potential to increase the effectiveness of immunotherapy. The early trial results suggest that the drug combination can indeed slow down cancer growth or even shrink tumours in some patients with aggressive brain cancers, who have few other treatment options available to them. 'Uncloaking the disease' Study leader Dr Juanita Lopez, Clinical Researcher at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said: “Brain cancer is able to evade the immune system in complex ways and, until now, immunotherapy has not worked. However, by uncloaking the disease using a new drug called ipatasertib, this study suggests that we could make some brain cancers vulnerable to atezolizumab. “We believe that our findings open the door to the further development of what could become a game-changing treatment option for some patients with aggressive glioblastoma brain cancer. Patients with glioblastoma have very poor survival rates, and even fewer new treatment options coming through, so any advance in outcomes would be extremely welcome.” Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, was also involved in the Ice-CAP study. He said: “Immunotherapy has had a dramatic effect on the treatment of some cancers, but with others such as brain tumours cancer cells seem to be successful at hiding from the immune system. These new preliminary trial results, although in just 10 patients, are exciting for showing the potential of immunotherapy to benefit patients with aggressive brain cancer when combined with a drug that effectively uncloaks the disease to the immune system. It’s great to see the benefits the combination has had already in a small number of patients who had run out of other options, and I hope that with further clinical development it can become an important new treatment for some patients.” 'It's astonishing that I'm still here' Hamish Mykura (59 from West Sussex) was first diagnosed with glioblastoma in August 2018 and was referred to The Royal Marsden for treatment, which included chemotherapy and radiotherapy, with surgery at St George's Hospital. When Hamish’s treatment stopped working and the cancer started to grow in August 2019, he joined the Ice-CAP trial. Some 20 months on, Hamish has shown a complete response with no visible cancer. He said: “The emotional journey I have been on over the last few years has been dramatic and, considering the seriousness of my diagnosis, it’s astonishing that I’m still here. In fact, a few months into the trial it felt like all hope had gone as it appeared my cancer had started growing again. However, surgery revealed the growth was actually inflammation caused by the drugs attacking the tumour - they were working. Ever since, I’ve been in a great position with scans indicating my cancer is stable. “Having the opportunity to take part in a clinical trial has been terrific and I now feel cautiously optimistic about the future. The cutting-edge science that has informed my treatment and care is truly remarkable. Thanks to The Royal Marsden and ICR, I’m feeling steadily better and, most importantly, able to spend time I didn’t think I’d have with my family.” This article was adapted from a news story on the ICR website.