OCEAN: a randomized Phase III study of melflufen + dexamethasone to treat relapsed refractory multiple myeloma

Schjesvold, Fredrik; Robak, Paweł; Pour, Luděk; Aschan, J; Sonneveld, Pieter

doi:10.2217/fon-2020-0024

Cited by 31 publications

(34 citation statements)

References 32 publications

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“…Treatment-related AEs associated with melflufen and dexamethasone are primarily hematologic, and rates of nonhematologic AEs are low. Based on the encouraging activity and acceptable safety profile of melflufen in RRMM, the randomized, head-to-head, superiority, open-label, global, Phase III OCEAN (OP-103) study is evaluating the efficacy and safety of melflufen plus dexamethasone versus pomalidomide plus dexamethasone in patients with RRMM who received two to four prior therapies including lenalidomide within 18 months and are refractory to the last line of therapy (Table 1) [32]. Top-line results for OCEAN are expected in the first half of 2021 [32].…”

Section: Discussionmentioning

confidence: 99%

“…Several novel drugs with new MOAs have been approved or are in development for RRMM, including selective inhibitors of nuclear export (selinexor), B-cell maturation antigen (BCMA)directed immunotherapies, and the PDC melflufen [23,32,33]. Selinexor is approved in the US in combination with dexamethasone to treat patients with RRMM who have received at least four prior therapies and who have disease that is refractory to at least two proteasome inhibitors, two IMiDs, and an anti-CD38 mAb [34,35].…”

Section: Therapies With New Moas For Rrmmmentioning

confidence: 99%

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Melflufen for relapsed and refractory multiple myeloma

Oriol

Larocca

Leleu

et al. 2020

Expert Opinion on Investigational Drugs

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Introduction: The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of standard-of-care agents such as immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies are increasingly used in earlier lines of therapy. Patients with disease that is refractory to multiple novel agents represent a population with high unmet medical need and for whom therapies with new mechanisms of action could be beneficial. Melphalan flufenamide (melflufen) has demonstrated encouraging activity in patients with relapsed and refractory multiple myeloma. Areas covered: This review provides an overview of the mechanism of action of melflufen, a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly delivers alkylating agents into tumor cells. It reviews key Phase I and II clinical trial data for melflufen in combination with dexamethasone as well as in triplet combinations with daratumumab or bortezomib. The safety profile of melflufen, which is characterized primarily by clinically manageable hematologic adverse events, is described. Expert opinion: Melflufen has potential to fill a gap in the myeloma treatment landscape by providing a new mechanism of action with clinically meaningful efficacy and a favorable safety profile in patients refractory to multiple novel agents.

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Section: Discussionmentioning

confidence: 99%

Section: Therapies With New Moas For Rrmmmentioning

confidence: 99%

Melflufen for relapsed and refractory multiple myeloma

Oriol

Larocca

Leleu

et al. 2020

Expert Opinion on Investigational Drugs

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“…For example, melflufen is a prodrug which is digested to melphalan by high levels of aminopeptidase in MM cells, thereby improving its therapeutic index. 149 , 150 Ultimately, the future use of novel targeted and immune therapies, as well as the role of conventional therapies, will be defined by vulnerabilities within individual patients and/or patient subgroups.…”

Section: Future Directionsmentioning

confidence: 99%

Multiple myeloma: the (r)evolution of current therapy and a glance into future

Gullà

Anderson

2020

haematol

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Over the past 20 years, the regulatory approval of several novel agents to treat multiple myeloma (MM) has prolonged median patient survival from 3 to 8-10 years. Increased understanding of MM biology has translated to advances in diagnosis, prognosis, and response assessment, as well as informed the development of targeted and immune agents. Here we provide an overview of the recent progress in MM, and highlight research areas of greatest promise to further improve patient outcome in the future.

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“…The preliminary data from the HORIZON study, demonstrating encouraging clinical efficacy and a manageable safety profile for melflufen plus dexamethasone [ 56 ], support the further development of this combination. Based on clinical data to date, OCEAN (OP-103; NCT03151811)—a randomized, head-to-head, superiority, open-label, global Phase III study of melflufen plus dexamethasone versus pomalidomide plus dexamethasone in patients with multiple myeloma who have received 2 to 4 prior therapies, including lenalidomide within 18 months and are refractory to last line of therapy—was initiated ( Table 4 ) [ 58 , 59 ].…”

Section: Additional Clinical Developmentmentioning

confidence: 99%

Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma

Mateos

Bladé

Bringhen

et al. 2020

JCM

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Despite the availability of new therapies that have led to improved outcomes for patients with multiple myeloma, most patients will eventually relapse. With triplet and even quadruplet combination therapies becoming standard in the first and second line, many patients will have few treatment options after second-line treatment. Melflufen (melphalan flufenamide) is a first-in-class peptide–drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Once inside the tumor cells, melflufen is hydrolyzed by peptidases to release alkylator molecules, which become entrapped. Melflufen showed anti-myeloma activity in myeloma cells that were resistant to bortezomib and the alkylator melphalan. In early phase studies (O-12-M1 and HORIZON [OP-106]), melflufen plus dexamethasone has demonstrated encouraging clinical activity and a manageable safety profile in heavily pretreated patients with relapsed/refractory multiple myeloma, including those with triple-class refractory disease and extramedullary disease. The Phase III OCEAN study (OP-104) is further evaluating melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma. The safety profile of melflufen is characterized primarily by clinically manageable hematologic adverse events. Melflufen, with its novel mechanism of action, has the potential to provide clinically meaningful benefits to patients with relapsed/refractory multiple myeloma, including those with high unmet needs.

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OCEAN: a randomized Phase III study of melflufen + dexamethasone to treat relapsed refractory multiple myeloma

Cited by 31 publications

References 32 publications

Melflufen for relapsed and refractory multiple myeloma

Melflufen for relapsed and refractory multiple myeloma

Multiple myeloma: the (r)evolution of current therapy and a glance into future

Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma

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