Daily Newsletter

24 May 2024

Daily Newsletter

ASCO 2024: Verastem’s combo therapy for pancreatic cancer hits early trial success

Shares in the pharma company rose 40% in pre-market trading.

Robert Barrie May 24 2024

Verastem Oncology has reported positive initial results from an ongoing Phase I/II trial investigating kinase inhibitor avutometinib for the treatment of pancreatic cancer.

The US biopharma company announced the initial interim safety and efficacy results as it gears up for a presentation at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting on 1 June 2024.

Verastem’s trial, named RAMP 205, is a single-arm study evaluating avutometinib plus defactinib in combination with gemcitabine and nab-paclitaxel, the latter two being standard-of-care chemotherapy, in patients with previously untreated metastatic pancreatic ductal adenocarcinoma.

Out of the six patients receiving 2.4mg avutometinib, five achieved a confirmed overall response rate (ORR). The 83% ORR exceeds other promising treatments in the space, including Jacobio Pharmaceutical’s glecirasib and Alligator Bioscience’s mitazalimab, amongst others.

Shares in the company rose 40% in premarket trading.

Patients in the dose level I cohort received 2.4mg of avutometinib twice a week and 200mg of defactinib twice a day for three weeks out of every four. Patients also were administered with 800mg/m² of gemcitabine and 125mg/m² of nab-paclitaxel on days one, eight and 15.

Avutometinib works by blocking both mitogen-activated protein kinase (MEK) kinase activity and rapidly accelerated fibrosarcoma’s (RAF) ability to phosphorylate MEK. The RAF/MEK clamp drug creates an anti-tumour response by inhibiting the RAS/MAPK pathway. Verastem says that its mechanism has an advantage over MEK-only inhibitors, as MEK signalling can be blocked without the compensatory activation of MEK, which can limit efficacy. Defactinib reduces tumour growth by blocking focal adhesion kinase (FAK).

Verastem’s chief medical officer John Hayslip said the trial results “are encouraging” and “demonstrate the importance of targeting the RAS/MAPK pathway, as more than 90% of pancreatic tumours have a KRAS mutation”.

Hayslip added: “We continue to progress the study evaluating other dose and schedule regimens to determine the recommended Phase II dose in the trial.”

Verastem gained an exclusive wordwide licence for avutometinib from Chugai Pharmaceuticals in January 2020. Defactinib was meanwhile licensed from Pfizer back in 2012.

Whilst Verastem touted positive efficacy results, the biopharma did report 19 treatment-emergent serious adverse events (SAEs) from 12 patients in the trial. 11 patients had Grade 3 or higher SAEs, including biliary obstruction, febrile neutropenia, and pulmonary embolism, amongst others. Two participants left the trial due to adverse events.

From the dose level 1 cohort, there was one case of dose-limiting toxicity of febrile neutropenia. Verastem stated the dose cohort was cleared after additional patients were evaluated.

Avutometinib won orphan drug designation from the US Food and Drug Administration (FDA) in March 2024. The agency designated the award for the treatment of recurrent low-grade serous ovarian cancer alone or with defactinib. Verastem’s has Phase II (NCT04625270) and Phase III (NCT06072781) trials ongoing for ovarian cancer treatment.

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