Updated Phase 3 Study Results Show Superior Progression-Free Survival with Melflufen in Multiple Myeloma
Despite the encouraging progression-free survival findings, data on overall survival resulted in a partial clinical hold instituted by the FDA.
Updated results from the phase 3 OCEAN study of melflufen plus dexamethasone have confirmed that the trial met its primary endpoint of superior progression-free survival (PFS) among patients with relapsed or refractory multiple myeloma who have received 2 to 4 prior lines of therapy.
The randomized OCEAN study was initiated in 2017 and includes 495 patients from more than 100 hospitals in 21 countries. Investigators evaluated the efficacy and safety of melflufen plus dexamethasone compared to pomalidomide plus dexamethasone. The topline results were announced May 25, 2021.
The updated results follow a blinded reassessment by the Independent Review Committee, which was not provided with all of the information available in the clinical database during their initial assessment.
According to a press release, this led to an investigation of all 495 patients for whom a comparison was made between the data provided to the committee and what data were available in the clinical database. During this process, the committee reassessed data from 29 patients. The findings confirmed that melflufen met the primary endpoint of superior PFS compared to pomalidomide with a hazard ratio of 0.792, according to the press release.
Overall survival (OS) was a key secondary endpoint, with a hazard ratio of 1.104 in favor of pomalidomide in the intention-to-treat population. According to the press release, the company has performed analyses of the OS data and believe that the results are attributable to substantial hazard ratio differences between pre-specified subgroups in both directions.
Based on these large differences in OS, the FDA has requested a partial clinical hold of all clinical studies with melflufen, pending further research. The company will cooperate with the FDA to perform necessary analyses to further understand the benefit/risk profile of melflufen and to identify which patients benefit from treatment in earlier lines of therapy, according to the press release.
Updated results from phase 3 OCEAN study shows melflufen met primary endpoint of superior PFS–Overall Survival data lead to partial clinical hold. News release. July 8, 2021. Accessed July 12, 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