A precision medicine targeting a key protein which helps cancer cells to tolerate DNA damage has shown promising results in two clinical trials.

The new findings demonstrate the safety of the drug, called SRA737, in a range of cancers and particular signs of effectiveness in advanced cancers of the anus and genitals – for which there are no effective treatment options.

The findings are being presented at the American Society of Clinical Oncology (ASCO) Annual Meeting – the world’s biggest cancer conference.

SRA737 targets a key cancer-related protein called Chk1, which is involved in cellular replication and cells’ response to DNA damage. It was discovered and initially developed by scientists at The Institute of Cancer Research, London, in collaboration with the company Sareum Holdings plc, and with funding from Cancer Research UK.

Two posters presented by Sierra Oncology – which holds the worldwide rights to develop and commercialise SRA737, and is leading its future development – gave the preliminary results of two separate international trials in a total of more than 250 patients.

Both phase I/II trials mostly involved patients from hospitals in the UK, and were led by Professor Udai Banerji, Deputy Director of the Drug Development Unit at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust.

One trialled SRA737 on its own and the other with low doses of a chemotherapy called gemcitabine. The chemotherapy ‘unlocks’ the biological effects of the new drug by causing DNA damage to cancer cells – making them more vulnerable to its effects.

The Chk1 protein can play a key role in cancer by preventing cells with damaged DNA from replicating their chromosomes and dividing. When it is blocked by SRA737, there is nothing to stop cancer cells progressing into replication and division – where the damage to DNA is picked up and triggers a cell-killing response.

In the trials, patients with several different cancer types responded to the drug. There were especially strong signs of effectiveness with the combination treatment in anogenital cancers where three out of 10 (30 per cent) responded.

Researchers also saw signs of effectiveness in patients with cancers with mutations in specific genes – and future trials will aim to confirm the drug’s effectiveness in these subtypes.

The results have led Sierra Oncology to propose further trials in advanced anogenital cancers, where SRA737 would represent a new option in a cancer of high unmet medical need.

Researchers are also exploring the future potential of SRA737 and low-dose gemcitabine combined with immunotherapy.

Recent data presented at last months’ American Association of Cancer Research (AACR) meeting, by researchers from the MD Anderson Cancer Center in Texas, showed promising results in mice for SRA737 in combination with anti-PD-L1 immunotherapies in small cell lung cancer.

Professor Udai Banerji, Deputy Director of the Drug Development Unit at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said:

“These studies have shown the potential of SRA737 as a possible future treatment for a range of cancer types, with some encouraging results in combination with low-dose chemotherapy in anogenital cancers."

“It’s a pleasure to see a drug discovered here at the ICR and progressed through development with our partners show potential as a future treatment. Hopefully, further trials will firmly establish the effectiveness of the drug and provide a new option for patients for whom new options are urgently needed.

‘’Now that the dose and schedules of administration have been established in cancer patients, it will be possible to explore further combinations of SRA737 with other drugs across different cancers where very interesting preclinical data has been seen.’’

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

“At the ICR, we believe that the future of cancer treatment is precision medicines, increasingly used as part of drug combinations, that exploit genetic weaknesses within cancer to overcome or delay drug resistance."

“The Chk1 inhibitor SRA737, which was discovered at the ICR with our partners Cancer Research UK and Sareum and is now being taken forward by Sierra Oncology, is an excellent example of such an innovative, highly targeted treatment."

“I am delighted to see the presentation of these results which indicate that SRA737 has the potential as part of combination therapy to benefit some patients with cancers of the anus and genitals – a group of diseases for which there are few therapeutic options.”

Source: ASCO