Immunotherapy combination presented at AACR meeting shows promise in brain cancers

pharmafile | April 12, 2021 | News story | Sales and Marketing Cancer Conferences | Cancer Conferences 2020 | Oncology Conferences | Oncology Conferences 2020 | International Cancer Conference 

Researchers at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust have found that immunotherapy together with a new experimental cancer drug could offer a new way of treating patients with aggressive brain cancers.

Early results from a Phase I clinical trial, which were presented at the American Association of Cancer Research (AACR) Annual Meeting on Saturday, 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, with one of these patients’ tumour disappearing completely.

Leader of the study, Dr Juanita Lopez, Clinical Researcher at The Institute of Cancer Research 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.”

The trial is supported by the immunotherapy Centers Of Research Excellence (imCORE) network, a Roche academic-industry partnership, and has recruited 10 patients with glioblastoma who had relapsed after treatment to the Phase I Ice-CAP trial.

Seven of the participants had tumours with defects in the PTEN gene and four patients had complete loss of PTEN expression. Data from the trial show that two out of four patients with complete PTEN loss responded to treatment.

The Ice-CAP trial 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.

One patient had aggressive brain cancer with faulty PTEN genes, and responded 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 have the ability to turn the anti-cancer immune response back up again, thereby giving it the potential to increase the effectiveness of immunotherapy.

Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, 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.”

Kat Jenkins

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