A pivotal Phase 3 study investigating melflufen (melphalan flufenamide) plus dexamethasone in people with relapsed or refractory multiple myeloma is fully enrolled, Oncopeptides, the treatment’s developer, announced.
The OCEAN trial (NCT03151811) recruited 450 patients across more than 100 clinical sites worldwide, and top-line results are expected later this year.
“I am very pleased to announce that we managed to complete enrollment in the OCEAN study despite the strenuous situation that our research and healthcare providers currently are facing,” Jakob Lindberg, CEO of Oncopeptides, said in a press release.
Melflufen belongs to a class of agents called peptidase-enhanced compounds that work through a new mechanism of action. Once inside a cell, melflufen is broken down by specific enzymes called aminopeptidases, releasing a toxic component that kills cells.
These enzymes are produced in excessive amounts by malignant cells, including those in multiple myeloma, meaning that melflufen preferentially targets and kills cancer cells.
Oncopeptides is planning to ask the U.S. Food and Drug Administration for melflufen’s accelerated approval for triple-refractory multiple myeloma patients, or those who failed to respond to treatment with at least one immunomodulatory drug, one proteasome inhibitor, and one anti-CD38 monoclonal antibody.
This submission, expected shortly, will be based on the HORIZON Phase 2 trial (NCT02963493), in which 26% of triple-refractory myeloma patients responded to the melflufen-dexamethasone combination.
HORIZON is evaluating the safety and efficacy of melflufen and dexamethasone in 157 multiple myeloma patients, including 119 with triple-refractory disease. These people had received at least two prior therapies, including an immunomodulatory agent and a proteasome inhibitor, and failed to respond to treatment with Darzalex (daratumumab) and/or Pomalyst (pomalidomide).
Final data from HORIZON showed that 86% of patients attained at least stable disease, including 29% of patients with partial or complete reductions in tumor burden. Responses were similar in patients with extramedullary disease (24%), an aggressive form of multiple myeloma in which myeloma cells form tumors outside the bone marrow, behaving like a metastatic cancer. These patients have a very poor prognosis.
Findings from HORIZON could be confirmed by those from OCEAN, which is investigating melflufen plus dexamethasone versus standard of care — Pomalyst and dexamethasone — in patients who received at least two but no more than four prior therapies. Previous treatments included Revlimid (lenalidomide) and a proteasome inhibitor, and patients were refractory (failed to respond) to Revlimid.
Participants were randomly assigned either melflufen every four weeks plus once-weekly dexamethasone, or Pomalyst on the first three weeks of a four-week cycle plus weekly dexamethasone. Treatment will be continued until disease progression, unacceptable toxicity, or patient withdrawal.
OCEAN’s main goal is to determine whether melflufen is better than Pomalyst, an oral immunomodulatory treatment, at extending the time patients live without disease worsening. Secondary objectives include overall response rate (the percentage of patients responding to treatment), duration of response, overall survival, and safety.
Findings from OCEAN are expected to support applications requesting melflufen’s marketing authorization in the U.S. and Europe for the treatment of relapsed or refractory myeloma.
“A positive OCEAN comparison between melflufen and the standard of care in RRMM [relapsed or refractory multiple myeloma] will provide critical insights on how to optimize treatment of RRMM patients,” Lindberg said.
“This comparison will enable us to file for label expansion of melflufen in the US and submit for regulatory approval in the EU and the rest of world,” he added.
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