The Institute of Cancer Research (ICR) has announced promising results from the Phase I PATRIOT trial of the new drug, ceralasertib, to treat patients with advanced solid tumours.
Administered as a pill, the drug targets the ataxia-telangiectasia mutated and RAD3-related (ATR) protein, crucial for cancer cell DNA repair. It could also enhance immune activity within tumours, potentially increasing their vulnerability to immunotherapy.
The study, which included 67 patients whose cancers had stopped responding to existing treatments, was conducted by a team at ICR and The Royal Marsden NHS Foundation Trust.
Funded by AstraZeneca, Cancer Research UK, and the Rosetrees Trust, the trial found that ceralasertib alone stabilised tumour growth in more than 50% of the patients.
The drug prevented disease progression for a minimum of four months in 68% of the 39 patients who benefited from the treatment.
An advanced ovarian cancer patient with ARID1A gene faults responded exceptionally well, with tumour reduction continuing for over five years.
Researchers conducted a comparative analysis of tumour biopsies before and after ceralasertib treatment to study the drug's biological impact.
They observed significant immune system changes in patients’ blood and tumours, suggesting that the drug may prime tumours for immunotherapy responsiveness.
Increased immune cell presence in the blood and tumour infiltration were noted, indicating an active attack on the tumours.
Previous clinical trials have shown ceralasertib's effectiveness when combined with PDL-1 inhibitors, a common immunotherapy, but this study is the first to demonstrate ceralasertib's immune-modulating properties as a standalone treatment.
Following the PATRIOT trial, additional studies have commenced, exploring ceralasertib in combination with other DNA repair inhibitors, such as olaparib.
The Institute of Cancer Research, London clinician scientist and The Royal Marsden NHS Foundation Trust clinical consultant and study leader Dr Magnus Dillon said: “This is the largest clinical trial of an ATR inhibitor, and it’s encouraging to see that on its own ceralasertib can keep cancer from progressing and even shrink patients’ tumours for an impressive time, giving some patients precious extra years of living well.
“Excitingly, this trial provides us with the biological insights for how best to combine this drug with an immunotherapy and generate an even more powerful cancer treatment for people who have exhausted other options.”
