The FDA have given the green light for Verastem Oncology’s combination therapy for KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC). The treatment, an oral combination of Avmapki (avutometinib) and Fakzynja (defactinib), is the first and only to be approved for the disease.
Avmapki plus Fakzynja was granted accelerated approval after Verastem’s Phase II RAMP 201 clinical study where it demonstrated a 44% overall response rate in LGSOC patients. Continued use of the therapy may be contingent upon verification from a confirmatory trial after the fact.
Rachel Grisham, Section Head of Ovarian Cancer at Memorial Sloan Kettering Cancer Center is the Global Lead Principal Investigator of the confirmatory Phase III trial: RAMP 301. She commented: “The combination of avutometinib and defactinib resulted in a significant overall response rate for patients with a KRAS mutation while being generally well tolerated.”
Grisham continued: “I look forward to progressing the confirmatory Phase III trial, RAMP 301, where we look to continue to support the ongoing body of research of this combination in women with and without a KRAS mutation.”
Both of the drugs involved in the trial are types of kinase inhibitor, which block cancer cell growth. Defactinib blocks FAK and PYK2 signalling pathways which avutometinib blocks the RAF/MEK pathways. Verastem’s combination therapy will be officially marketed under the name AVMAPKI FAKZYNJA CO-PACK.
“Today’s approval […] represents not only the first-ever FDA-approved treatment specifically for this rare cancer but also a new day for people living with this disease who have been in desperate need of new treatment options,” said Dan Paterson, President and Chief Executive Officer of Verastem Oncology.
Verastem started a rolling new drug application (NDA) with the FDA in May 2024 and finalised its submission in October 2024. The FDA granted Priority Review, resulting in approval before the Prescription Drug User Fee Act (PDUFA) action date of June 30, 2025.