FDA Calls For Partial Clinical Hold on Trial Evaluating Melflufen in Relapsed/Refractory Multiple Myeloma
A trial evaluating melflufen in myeloma met its primary end point of progression free survival in the phase 3 OCEAN trial; however, overall survival was in favor of pomalidomide.
Following a blinded reassessment by the Independent Review Committee (IRC), the FDA has requested that oncopeptides AB agree to a partial pause in clinical studies involving melflufen (melphalan flufenamide). Oncopeptides will collaborate with the FDA to continue to uncover the benefits and risks associated with the agent and its impact in the treatment of relapsed refractory multiple myeloma.
Melflufen demonstrated superior progression free survival (PFS) compared to pomalidomide with a hazard ratio (HR) of 0.792 in the recent phase 3 OCEAN Study. However, upon reviewing the overall survival (OS) data, the FDA has requested the partial clinical hold.
OS, a secondary endpoint in the OCEAN study, induced an HR of 1.104 in favor of pomalidomide for the intention-to-treat population.
Melphalan targets the overexpressed aminopeptidases in multiple myeloma cells, which are associated with advanced disease and tumor mutational burden. By targeting aminopeptidases, the drug attempts to spare the healthy cells by initiating selective activity in the cancer cells.
Oncopeptides updated results and safety measures based on data from the head-to-head phase 3 Ocean study. The study measured the efficacy and safety of the combination of melfulufen plus dexamethasone against the combination of pomalidomide plus dexamethasone in patients with relapsed refractory multiple myeloma. There were 495 participants in total, from more than 100 hospitals across 21 different countries. Each patient had received 2 to 4 lines of therapy prior to the study.
The study began in 2017 and topline results were declared on May 25.
When preparing the clinical study report and regulatory documents, it became clear that the IRC was not provided with all necessary clinical database information at the time of their initial assessment, and, therefore, the data of 29 patients needed to be reassessed.
Oncopeptides has “performed analyses of the OS data and the company believes that the OS results are primarily explained by substantial HR differences between pre-specified subgroups in both directions,” the company stated in a news release.
Further investigation will determine whether melflufen will continue to be studied in clinical trials. In the meantime, oncopeptides plans to work with the FDA to expeditiously analyze the safety and efficacy of the drug.
Oncopeptides News Release. Updated results from phase 3 OCEAN study shows melflufen met primary endpoint of superior PFS – Overall Survival data lead to partial clinical hold. Published: July 8, 2021. Accessed July 8, 2021. https://www.oncopeptides.com/en/media/press-releases/updated-results-from-phase-3-ocean-study-shows-melflufen-met-primary-endpoint-of-superior-pfs--overall-survival-data-lead-to-partial-clinical-hold.