The first clinical trial of a new precision medicine that stops cancer from repairing its DNA has shown promising results, it was revealed last night.
The phase I trial, led by the Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, examined the efficacy of berzosertib, an ATR inhibitor, either on its own or with chemotherapy in 38 patients with very advanced tumours.
They reported that 20 of the participants, who were being treated in hospitals around the world, saw their tumours shrinking if they had the new drug on its own or with platinum chemotherapy, while two patients saw their tumours shrink or disappear completely.
The study team also discovered that the drug’s benefit in blocking DNA repair was even more marked in patients also given chemotherapy. In these patients, 15 out of the 21 (71%) saw their disease stabilise, which suggested that chemotherapy boosted sensitivity to berzosertib.
Writing in today’s edition of the Journal of Clinical Oncology, the researchers also described how one patient with advanced bowel cancer, whose tumour contained faults in key DNA repair genes including CHEK1 and ARID1A, responded well to berzosertib on its own. His tumours disappeared and he remained cancer free for more than two years.
Another woman with advanced ovarian cancer, whose disease returned following treatment with a drug-blocking PARP, saw her tumours shrink after receiving the combination treatment, suggesting that berzosertib could be explored as a strategy to overcome resistance to the PARP inhibitor family of targeted treatments.
Professor Johann de Bono, head of drug development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said: “Our new clinical trial is the first to test the safety of a brand new family of targeted cancer drugs in people, and it’s encouraging to see some clinical responses even in at this early stage. Now, we and others are planning further clinical trials of berzosertib and other drugs blocking the ATR protein.
“In future, this new class of ATR inhibiting drugs could boost the effect of treatments like chemotherapy that target cancer DNA, expand our range of treatment options and overcome resistance to other targeted treatments.”
Professor Paul Workman, chief executive of The Institute of Cancer Research, London, added: “It’s exciting to see the first clinical trial of a drug targeting a key player in the DNA repair process have such promising results, and I look forward to the results of further studies testing the benefit of this new family of targeted treatments.”
Journal of Clinical Oncology 22 June 2020
Leave a Reply