ICR study combines precision medicines to treat drug-resistant cancers

Results from an early-stage trial demonstrate that using a combination of two precision medicines to target hard-to-treat cancers was safe and showed promise in a range of solid tumour types.

The trial, led by a team at the Institute of Cancer Research (ICR) in London and the Royal Marsden NHS Foundation Trust, combined AstraZeneca/Merck’s PARP inhibitor Lynparza (olaparib) with the investigational medicine capivasertib, an AKT Kinase inhibitor.

The researchers used the drug combination to target two weaknesses in cancer, namely a damaged system for repairing DNA and ‘addiction’ to the AKT molecule which fuels tumour growth.

In the Phase I trial, researchers gave 64 patients with advanced solid tumours, including those with breast cancer, ovarian cancer and prostate cancers, combinations of Lynparza and capivasertib.

The trial found that the drug combination was safe to use and also efficiently hit the specified targets, and showed promise against a variety of advanced cancers, including those that had become resistant to chemotherapy.

According to the ICR, many of the patients who responded to the treatment had mutations in the genes involved in repairing DNA, including the BRCA genes.

“This new clinical trial is a terrific example of how we can now translate scientific discoveries about the biology of cancer cells into innovative new cancer treatments with real benefits for patients,” said Professor Paul Workman, Chief Executive of the ICR.

“It’s also an example of the pioneering strategy we have adopted at the ICR of targeting cancer evolution and drug resistance – often through the use of combination treatments to hit multiple targets at once and block off escape routes, just as is done with diseases like HIV,” he added.

The trial was funded by AstraZeneca, with the backing of the Cancer Research UK Experimental Cancer Medicine Centre Combinations Alliance.

Following the promising early results, later-stage clinical trials are planned to assess the drug combination’s benefit and to study its effect in patients whose tumours do not have faults in the AKT gene or related to DNA repair.