Researchers from the Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust have revealed that AstraZeneca’s (AZ) ceralasertib (AZD638) showed promise in patients no longer responding to current cancer treatments.
Published in the Journal of Clinical Investigation, the early-stage PATRIOT trial was funded by AZ, Cancer Research UK and the Rosetrees Trust.
Immunotherapies are drugs that harness the body’s own immune system to fight a variety of cancers.
Researchers treated 67 patients living with advanced solid tumours where other treatments had stopped working and their tumours were continuing to grow with ceralasertib, an oral ATR kinase inhibitor, and compared tumour biopsies taken before and after treatment.
The team saw that the drug on its own caused significant changes in patients’ immune systems, both within their tumours and blood, as well as its impact on DNA repair.
Results from the study showed that the drug stopped tumour growth in more than half of the patients, and in five patients, ceralasertib shrank their tumours.
Furthermore, a single patient living with advanced ovarian cancer whose tumour had faults in the key DNA repair gene, ARID1A, saw their tumour shrink over a period of more than five years.
Out of the 39 patients who benefitted from the drug, 68% saw zero progression of their disease for at least four months.
Researchers also observed that the drug increased a type of immune cell that seeks out and eliminates cancer cells in the blood, along with increased infiltration of immune cells into the tumours, suggesting that they would be responsive to a variety of immunotherapies.
The ICR and Royal Marsden are currently undergoing other clinical trials to investigate the use of cerlasertib in combination with other drugs that prevent DNA from repairing itself, including AZ’s and Merck & Co’s PARP inhibitor Lynparza (olaparib).
“Ceralasertib can keep cancer from progressing and even shrink patients’ tumours for an impressive time” and has “given us a clue as to the biological markers which may predict who could benefit from this drug in [the] future,” said Dr Magnus Dillon, clinician scientist, ICR and clinical consultant, Royal Marsden NHS Foundation.