Positive topline results of the phase III OCEAN study of melflufen for RRMM

On May 25, 2021, positive topline results from the phase III OCEAN study (NCT03151811) of melphalan flufenamide (melflufen) for the treatment of relapsed/refractory multiple myeloma (RRMM) were released. These results demonstrated that melflufen was at least as efficacious as pomalidomide for this indication.¹

Melflufen¹

• A peptide-drug conjugate/prodrug of melphalan that is more readily taken up by cells than melphalan.
• It was granted accelerated approval by the US Food and Drug Administration (FDA) in combination with dexamethasone earlier this year for the treatment of adult patients with RRMM who have received ≥4 prior lines of therapy and who are refractory to ≥1 proteasome inhibitor, immunomodulatory agent, and CD38-directed monoclonal antibody.

OCEAN study (NCT03151811)^1,2

• A randomized, multicenter, open-label, phase III study evaluating the safety and efficacy of melflufen + dexamethasone compared with pomalidomide + dexamethasone in patients with RRMM.
• Start date: June 12, 2017.
• Estimated completion: July 2022.
• Enrollment: 495 adult patients who had 2–4 prior lines of therapy and were refractory to lenalidomide in the last line of therapy.
• Dosage: 40 mg melflufen on Day 1 + 40 mg dexamethasone on Days 1, 8, 15, and 22 of each 28-day cycle; or 4 mg pomalidomide on Days 1–21 + 40 mg dexamethasone on Days 1, 8, 15, and 22 of each 28-day cycle. Patients aged ≥75 years had a reduced dose (20 mg) of dexamethasone.
• Primary outcome measure: progression-free survival (PFS).
• Secondary outcome measures: overall response rate (ORR), duration of response, overall survival, safety, and tolerability.

Results¹

• Assessment by the Independent Review Committee demonstrated melflufen was non-inferior to pomalidomide in terms of PFS, with a hazard ratio (HR) favoring melflufen (HR, 0.817; 95% confidence interval [CI], 0.659–1.012, p = 0.0640).
  • The median PFS was 41% higher for melflufen vs pomalidomide.
• Investigator assessment showed melflufen was superior to pomalidomide in terms of PFS, with a HR favoring melflufen (HR, 0.790; 95% CI, 0.639–0.976).
  • The median PFS was 42% higher for melflufen vs pomalidomide.
• The ORR was also slightly higher for melflufen compared with pomalidomide (32.1% vs 26.5%, respectively).
• Similar discontinuation rates for adverse events were observed for both arms.
• The safety profile of melflufen was in line with previous studies and consistent across age subgroups.

Based on these data, a supplementary new drug application to move to earlier lines of therapy is planned to be submitted to the FDA in the last quarter of 2021.