FDA Has Requested a Partial Clinical Hold on All Trials With Melflufen in Following Study in R/R Myeloma

The FDA has requested a partial clinical hold on all trials featuring melflufen following the updated results of the phase 3 OCEAN study in relapsed/refractory multiple myeloma.

The FDA has requested a partial clinical hold on all trials of melphalan flufenamide (melflufen; Pepaxto) following updated results of the phase 3 OCEAN study (NCT03151811), which examined the agent in combination with dexamethasone vs pomalidomide (Pomalyst)/dexamethasone in relapsed/refractory multiple myeloma, according to a press release from drug developer Oncopeptides AB.1

Although the trial met its primary end point of superior progression-free survival (PFS) with melflufen vs the pomalidomide combination as assessed by independent review committee (IRC; HR, 0.792; 95% CI, 0.640-0.979; P = .0311), the key secondary end point of the trial, overall survival (OS), favored the control arm (HR, 1.104; 95% CI, 0.846-1.441). These findings led the FDA to request a partial clinical hold on all studies of melphalan until further investigation can confirm large OS differences observed in certain patient subgroups.

The study featured patients (n = 495) with relapsed/refractory disease who underwent 2 to 4 prior lines of therapy. It was initiated in 2017 and was conducted across 21 countries and in more than 100 hospitals. The updated results of the study were the result of a blinded reassessment by IRC. However, while preparing the clinical study report and regulatory documents, it was found that the IRC was not given all the necessary information that was available in the clinical database at the time of initial assessment.

Due to this, a thorough investigation took place of all patients enrolled on the study, wherein a comparison was established between the data provided to the IRC and that which was available in the clinical database. Data from 29 patients needed to be reexamined. Oncopeptides conducted an OS analysis and stated that the results could notably be due to the significant differences in HR between pre-specified subgroups on both sides.

Initial results from the OCEAN study were reported in May 2021 showing that melflufen was noninferior to pomalidomide in patients with relapsed/refractory disease.2 Notably, the median PFS by IRC was 42% higher in the melflufen arm vs the pomalidomide arm, with an overall response rate of 32.1% and 26.5% in both arms, respectively.

Oncopeptides plans to cooperate closely with the FDA in order to perform the needed analysis to fully assess the risk/benefit profile of melflufen and get a better understanding of which patients with multiple myeloma will benefit from treatment in earlier lines of therapy within the relapsed/refractory setting.


  1. 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. Oncopeptides AB. July 8, 2021. Accessed July 8, 2021. https://bit.ly/3qUzUR2
  2. Oncopeptides AB: Phase 3 OCEAN study demonstrates that melflufen is at least as efficacious as pomalidomide, the most used medicine in relapsed refractory multiple myeloma. News release. Oncopeptides AB. May 25, 2021. Accessed July 8, 2021. https://prn.to/3AJPiUP
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