Recently, data from a study published by the Royal Marsden Cancer Centre showed promising data on the combination of Avutometinib + Defactinib for ovarian cancer, resulting in significant tumour shrinkage in 28% of patients and disease control in 93% of patients.
Based on interim data from the Phase 2 RAMP-201 trial, the combination of Avutometinib and Defactinib was effective in treating recurrent low-grade plasmacytoma ovarian cancer.
In this trial, the two-drug combination resulted in significant tumour shrinkage in 28% of patients. Among patients with KRAS mutations, 27% had significant tumour shrinkage; among patients with KRAS wild-type, 29% had significant tumour shrinkage. In addition, a total of 93% of patients had controlled disease without further progression.
In contrast, 7% of patients treated with Avutometinib monotherapy had significant tumour shrinkage and up to 90% of patients had disease control.
In terms of safety, common treatment-related adverse reactions caused by the combination therapy in all patients treated included diarrhoea, nausea, elevated blood creatine phosphokinase, blurred vision, acne-like dermatitis and rash, fatigue and peripheral oedema, with most symptoms being mild to moderate.
"Interim data from the ongoing Phase 2 RAMP-201 trial show that the combination of Avutometinib and Defactinib produced encouraging efficacy and a favorable safety profile in patients with recurrent low-grade plasma ovarian cancer who have received extensive prior treatment." Dr Susana Banerjee of the Royal Marsden Cancer Centre, the study's global principal investigator, said, "The tumour shrinkage rates in KRAS mutant and KRAS wild-type patients with the combination of Avutometinib and Defactinib and the high disease control data observed to date are very important , which supports the continued use of this combination regimen."
Dr Susana Banerjee
Avutometinib is a dual MEK/RAF inhibitor that induces inactive complexes of MEK with ARAF, BRAF, and CRAF, producing a more complete and long-lasting anti-tumour effect by assuming greater inhibition of the RAS pathway.
RAMP-201 is an ongoing multicentre, parallel cohort, randomised, open-label trial comparing the safety and efficacy of Avutometinib monotherapy and Avutometinib + Defactinib combination therapy in patients with recurrent low-grade plasmacytotic ovarian cancer. Part A aims to determine whether the best option is monotherapy or combination therapy. The treatment approach in the extension phase will be based on the results of the data from Part A.
The trial is being conducted at multiple sites around the world, including Memorial Sloan Kettering Cancer Center and Cleveland Medical Center in the US, and the Royal Marsden Cancer Centre in the UK, and is still recruiting patients.
