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September 20, 2021

ICR says drug combo demonstrates effectiveness in ovarian cancer trial

Nearly 46% of LGSOC patients had substantial tumour shrinkage on receiving treatment with VS-6766 and defactinib. 

The Institute of Cancer Research (ICR), London has reported that a novel combination of targeted drugs demonstrated to be effective in shrinking tumours in half of the patients with low-grade serous ovarian cancer (LGSOC) in the Phase I FRAME clinical trial.

The treatment combination comprised VS-6766 and defactinib, which can potentially hinder signals that cancer cells require to grow.

VS-6766 is a dual RAF/MEK inhibitor of Verastem Oncology while defactinib is a FAK inhibitor.

Led by a team at the ICR and The Royal Marsden NHS Foundation Trust, the investigator-initiated trial analysed the drugs in 25 subjects with low-grade serous ovarian cancer.

Researchers found that VS-6766 remains active in the body for a longer time and can be administered twice-weekly to offer its potent anti-tumour effects while reducing side effects. Defactinib was given twice daily to the subjects.

The findings showed that overall, approximately 46% of patients had substantial tumour shrinkage in response to the treatment with the combination drugs.

In subjects with KRAS gene mutation, more favourable responses were observed. KRAS is the most common gene mutations in cancer, seen in one-quarter of all tumours.

Furthermore, the trial data showed that about 64% or two-thirds of subjects with a KRAS mutation has tumour shrinkage on receiving the treatment.

This indicates that tumour profiling could be utilised to detect patients who could potentially benefit from treatment with the new drug combination.

The subjects survived for an average of 23 months before cancer progression, which is not usual to report such positive clinical responses in Phase I trials.

The Phase I trial assessed the safety of the combination drugs and intended to establish the tolerated dose without unmanageable side effects.

ICR London Women’s Cancers team leader Dr Susana Banerjee said: “If these findings are confirmed in larger trials, they’ll represent a significant advance in low-grade serous ovarian cancer treatment.

“I am delighted that this drug combination has worked so well in a group of patients who are in urgent need of new treatments, including those who have previously been treated with a MEK inhibitor.”

A Phase II trial sponsored by Verastem is currently progressing global recruitment to assess the efficacy of the combination treatment.

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