The combination of INN melphalan flufenamide and dexamethasone was found to induce a superior progression-free survival benefit over pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma who had previously received 2 to 4 lines of therapy, meeting the primary end point of the phase 3 OCEAN trial.
The combination of INN melphalan flufenamide (Melflufen) and dexamethasone was found to induce a superior progression-free survival (PFS) benefit over pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma who had previously received 2 to 4 lines of therapy, meeting the primary end point of the phase 3 OCEAN trial (NCT03151811).1
However, the FDA has requested that a partial hold be placed on all clinical studies examining the agent, pending further investigation, due to differences in overall survival (OS) observed in prespecified patient subgroups.
The updated findings follow a blinded re-assessment that was conducted by an independent review committee. When compiling the report on the trial and other regulatory documents it became clear that the committee was not given all the information that was available in the clinical database at the time of the first assessment, according to Oncopeptides AB.
As such, an investigation was launched to compare the data on all 495 participants that had been provided to the committee with the information that was available in the database. It was determined that 29 patients needed to be reassessed.
Data from the final analysis of the trial found that the melphalan flufenamide arm was superior to the control arm regarding PFS in this population (hazard ratio [HR], 0.792; 95% CI, 0.640-0.979; P = .0311). However, the HR for OS was 1.104 (95% CI, 0.846-1.441) and favored the pomalidomide/dexamethasone arm in the intention-to-treat population.
“Oncopeptides has performed analyses of the OS data and the Company believes that the OS results are primarily explained by substantial HR differences between prespecified subgroups in both directions,” according to a recent press release.
The global biotechnology company stated that they will work closely with the FDA to rapidly conduct an analysis that will help provide insight into the benefit/risk profile of melphalan flufenamide and to determine which patients with relapsed/refractory multiple myeloma will benefit from treatment with the agent in earlier lines of therapy.
The global, head-to-head, open-label, phase 3 OCEAN trial examined the safety and efficacy of melphalan flufenamide plus dexamethasone vs pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma who had previously received 2 to 4 therapies.
Participants received prior treatment with at least 1 immunomodulatory drug (IMiD) and 1 proteasome inhibitor (PI). Moreover, all had developed resistance to lenalidomide (Revlimid) and the last line of therapy that they had received. If patients received prior pomalidomide, they were excluded from the trial.
The primary end point was PFS, and key secondary end points comprised objective response rate (ORR), duration of response (DOR), and OS.
Earlier data from the trial showed that melphalan flufenamide plus dexamethasone elicited an ORR of 32.1% vs 26.5% with pomalidomide and dexamethasone.2
Discontinuation rates due to adverse effects were found to be similar between the investigative and control arms. The safety profile of melphalan flufenamide was consistent with what had previously been observed in trials examining the agent, and it was also consistent across age subsets.
In February 2021, the FDA gave the green light to melphalan flufenamide for use in combination with dexamethasone in patients with relapsed/refractory multiple myeloma who had previously received at least 4 lines of therapy and whose disease was refractory to at least 1 PI, 1 IMiD, and 1 CD38-targeted monoclonal antibody.3
The regulatory decision was supported by data from the phase 2 HORIZON trial (NCT02963493), where the combination induced an ORR of 23.7%, with a median DOR of 4.2 months in this heavily pretreated population.4