Promising Pancreatic Cancer Treatment Receives FDA Orphan Drug Designation
Avutometinib plus defactinib shows promising early results in pancreatic cancer, earning an orphan drug designation from the FDA.
Microscopic image of pancreatic cancer cells - Generated with Google Gemini AI
- The FDA has granted an orphan drug designation to avutometinib (VS-6766) plus defactinib (VS-6063) for the treatment of pancreatic cancer.
- With this designation, Verastem Oncology, the sponsor, is eligible for tax credits, exemptions from FDA user fees, and market exclusivity for 7 years.
- The combination has also been investigated for the treatment of ovarian cancer.
The combination of avutometinib, an RAF/MEK clamp, and defactinib, a selective FAK inhibitor, has been granted orphan drug designation from the FDA for the treatment of patients with pancreatic cancer.1
Orphan drug designation is given to new treatments that prevent, diagnose, or treat rare conditions. With this designation, Verastem Oncology, the sponsor, will be eligible for tax credits for qualified clinical trials, exemption from user fees, and a potential of 7 years of market exclusivity following approval.
Updated findings from the phase 1b/2 RAMP 205 (NCT05669482) evaluating the combination were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. As of the data cutoff of May 14, 2024, there were 41 patients treated in 1 of 4 dose cohort regimens. Only patients in dose cohort 1 had a minimum follow-up of 6 months.
Among those in dose level 1, 5 of the 6 (83%) patients had a confirmed partial response (PR) with more than 6 months of follow-up at the time of data cutoff. There was 1 dose-limiting toxicity (DLT) seen in this cohort. The dose level was then cleared following the enrollment of additional patients. In all cohorts, 21 of the 26 patients who had the opportunity to have their first scan while on treatment have had a reduction of the change in target lesion sum of diameters.
"At the ASCO 2024 Annual Meeting, we reported positive initial interim results from the ongoing RAMP 205 trial evaluating avutometinib and defactinib in combination with standard of care chemotherapy in first-line metastatic pancreatic cancer," said Dan Paterson, president and chief executive officer of Verastem Oncology, in a press release.1
Previously at a cutoff date of January 24, 2024, no DLTs were reported, and most treatment-related adverse events (TRAEs) were mild to moderate.2 The most common TRAEs among the patient population (n = 18) were nausea (50%), alopecia (44%), fatigue (39%), maculo-papular rash (33%), and peripheral edema (28%). For grade 3 or higher TRAEs, the most common included alanine aminotransferase increase (17%), neutropenia (17%), peripheral edema (11%), anemia (11%), and sepsis (11%).
Microscopic image of pancreatic cancer tumor - Generated with Google Gemini AI
Efficacy was evaluable in 8 patients, and all experienced a reduction in target lesions for a 100% disease control rate (DCR). PRs were observed in 75% of patients (n = 6).
“We believe avutometinib and defactinib in combination with standard of care has an opportunity to provide a different approach in treating this challenging cancer. We look forward to reporting updated data from across dose cohorts in the ongoing RAMP 205 trial in the first quarter of 2025," continued Paterson.1
In March 2024, the FDA also granted avutometinib alone or in combination with defactinib an orphan drug designation for the treatment of patients with recurrent low-grade serous ovarian cancer, a subtype of the disease with no currently approved treatments.3
About the RAMP 205 Study
The RAMP 205 study has an estimated enrollment of 40 patients with previously untreated pancreatic ductal adenocarcinoma across 12 locations.4 The study’s primary end points are assessment of DLTs and overall response rate. Secondary end points include duration of response, DCR, progression-free survival, overall survival, pharmacokinetics, incidence of AEs, and incidence of abnormal laboratory values.
Patients will be treated with gemcitabine and nab-paclitaxel plus avutometinib and defactinib. The study is currently enrolling and has an estimated completion date of December 31, 2025.
