A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide

NCT03151811 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: OP-103
• Study Type: interventional
• Target: 495
• Locations: 20 countries
• Sites: 103

Brief Summary

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with RRMM following 2-4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide. Patients received either melflufen+dex or pomalidomide+dex.

Conditions

Multiple Myeloma

Keywords

Refractory Multiple Myeloma; Relapsed Multiple Myeloma; Melphalan flufenamide (Melflufen); Pomalidomide; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression Free Survival defined as the duration in months from randomization until first evidence of confirmed disease progression, as assessed by the Independent Review Committee (IRC) according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Disease progression was defined according to the IMWG-URC as progressive disease or death due to any cause, whichever occurs first.

  From date of randomization until first evidence of confirmed disease progression or death due to any cause (whichever occurred first), up to the data cutoff date of 03 Feb 2021 (ie, assessed up to approximately 43 months).

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  From randomization until best response achieved before confirmed disease progression or death due to any cause, up to data cutoff of 03 Feb 2021 (ie, assessed up to approx. 43 months). Median time to best response: Arm A=2.1 months and Arm B=2.0 months

• Duration of Response (DOR)

  From first documentation of a confirmed response to first evidence of confirmed disease progression or death due to any cause, up to the data cutoff date of 03 Feb 2021 (ie, assessed up to approximately 43 months).

• Overall Survival (OS)

  From date of randomization until up to 24 months following confirmed disease progression or initiation of subsequent therapy, up to the data cutoff date of 03 Feb 2023 (ie, assessed up to approximately 67 months).

• Safety and Tolerability: Number of Patients With Treatment-emergent Adverse Events (TEAEs), Including Clinical Laboratory and Vital Signs Abnormalities, as Assessed by CTCAE v4.0

  From start of dosing until 30 days after the last dose of study treatment, up to the data cutoff date of 03 Feb 2023 (ie, assessed up to approximately 67 months). Median duration of study treatment was 25.2 and 22.1 weeks for Arm A and B, respectively.

Study Arms (2)

Arm A: Melflufen+Dexamethasone

EXPERIMENTAL

Melflufen 40 mg i.v. on Day 1 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.

Drug: Melflufen; Drug: Dexamethasone

Arm B: Pomalidomide+Dexamethasone

ACTIVE COMPARATOR

Pomalidomide 4 mg orally daily on Days 1 to 21 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.

Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Melflufen DRUG

Intravenous infusion

Also known as: Melphalan Flufenamide, Pepaxti

Arm A: Melflufen+Dexamethasone

Pomalidomide DRUG

Oral capsules

Also known as: Pomalyst, Imnovid

Arm B: Pomalidomide+Dexamethasone

Dexamethasone DRUG

Oral tablets

Also known as: Dex, Fortecortin, Decadron

Arm A: Melflufen+Dexamethasone; Arm B: Pomalidomide+Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 years or older
• A prior diagnosis of multiple myeloma with documented disease progression requiring further treatment at time of screening
• Measurable disease defined as any of the following:
• Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis.
• ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis
• Serum free light chain ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
• Received 2-4 prior lines of therapy, including lenalidomide and a PI, either sequential or in the same line, and is refractory (relapsed and refractory or refractory) to both the last line of therapy and to lenalidomide (≥ 10 mg) administered within 18 months prior to randomization. Refractory to lenalidomide is defined as progression while on lenalidomide therapy or within 60 days of last dose, following at least 2 cycles of lenalidomide with at least 14 doses of lenalidomide per cycle.
• Life expectancy of ≥ 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to start of treatment. Participants must agree to ongoing pregnancy testing. All patients must be willing to comply with all requirements of the USA pomalidomide Risk Evaluation and Mitigation Strategy (REMS) program or the pomalidomide Pregnancy Prevention Plan (PPP).
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent.
• lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec Fridericia Formula.
• The following laboratory results must be met during screening and also immediately before study drug administration on Cycle 1 Day 1:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3 (1.0 x 10\^9/L)
• Platelet count ≥ 75,000 cells/mm\^3 (75 x 10\^9/L)

You may not qualify if:

• Primary refractory disease (i.e. never responded (≥ MR) to any prior therapy)
• Evidence of mucosal or internal bleeding or platelet transfusion refractory
• Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.
• Prior exposure to pomalidomide
• Known intolerance to IMiDs.
• Known active infection requiring parenteral or oral anti-infective treatment within 14 days of randomization.
• Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance.
• Pregnant or breast-feeding females
• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
• Known human immunodeficiency virus or active hepatitis C viral infection
• Active hepatitis B viral infection (defined as HBsAg+).
• Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-).
• Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the discretion of the investigator after consideration of risk of reactivation.
• Concurrent symptomatic amyloidosis or plasma cell leukemia
• POEMS syndrome

Sponsors & Collaborators

• Oncopeptides AB: lead

Study Sites (105)

US17

Tucson, Arizona, 85711, United States

Location

US01

Fresno, California, 93710, United States

Location

US11

Gainesville, Florida, 32610, United States

Location

US12

Orange City, Florida, 32763, United States

Location

US-19

Plantation, Florida, 33324, United States

Location

US16

Boise, Idaho, 83712, United States

Location

US-24

Louisville, Kentucky, 40207, United States

Location

US13

Boston, Massachusetts, 02215, United States

Location

US-27

Hattiesburg, Mississippi, 39401, United States

Location

US-21

Salisbury, North Carolina, 28144, United States

Location

US-30

Winston-Salem, North Carolina, 27103, United States

Location

US06

Philadelphia, Pennsylvania, 19107, United States

Location

US15

Fort Sam Houston, Texas, 78234, United States

Location

US-18

Temple, Texas, 76504, United States

Location

AT-02

Linz, Austria

Location

AT-01

Vienna, Austria

Location

BE-05

Edegem, Belgium

Location

BE-03

Liège, Belgium

Location

BE-02

Roeselare, Belgium

Location

CZ-05

Brno, Czechia

Location

CZ-03

Hradec Králové, Czechia

Location

CZ-04

Olomouc, Czechia

Location

CZ-01

Ostrava, Czechia

Location

Cz-02, Cz-06

Prague, Czechia

Location

DK01

Vejle, Denmark

Location

EE-01

Tallinn, Estonia

Location

EE-02

Tartu, Estonia

Location

FR04

Brest, France

Location

FR-11

Cholet, France

Location

FR01

Le Mans, France

Location

FR05

Limoges, France

Location

FR-07

Lyon, France

Location

FR06

Lyon, France

Location

FR03

Mulhouse, France

Location

FR-09

Nice, France

Location

FR-10

Périgueux, France

Location

FR-08

Poitiers, France

Location

Gr02, Gr03

Athens, Greece

Location

GR04

Pátrai, Greece

Location

GR01

Thessaloniki, Greece

Location

Hu02, Hu03, Hu04

Budapest, Hungary

Location

HU01

Debrecen, Hungary

Location

HU-06

Kaposvár, Hungary

Location

HU-05

Pécs, Hungary

Location

IL03

Jerusalem, Israel

Location

IL01

Nahariya, Israel

Location

IL05

Rehovot, Israel

Location

IL02

Safed, Israel

Location

IL04

Tel Aviv, Israel

Location

IL06

Tel Aviv, Israel

Location

IT07

Bergamo, Italy

Location

IT02

Bologna, Italy

Location

IT08

Brescia, Italy

Location

It03, It09

Milan, Italy

Location

IT06

Modena, Italy

Location

IT04

Piacenza, Italy

Location

IT05

Terni, Italy

Location

IT01

Torino, Italy

Location

LT-02

Kaunas, Lithuania

Location

LT-01

Vilnius, Lithuania

Location

NL01

Rotterdam, Netherlands

Location

NO-02

Ålesund, Norway

Location

NO01

Oslo, Norway

Location

PL03

Bialystok, Poland

Location

PL02

Chorzów, Poland

Location

PL06

Lodz, Poland

Location

PL05

Lublin, Poland

Location

PL-08

Olsztyn, Poland

Location

PL07

Poznan, Poland

Location

PL04

Rzeszów, Poland

Location

PL-09

Torun, Poland

Location

RO-02

Brasov, Romania

Location

RO-01

Bucharest, Romania

Location

RU-04

Izhevsk, Russia

Location

Ru-11, Ru-14

Krasnoyarsk, Russia

Location

RU-03

Moscow, Russia

Location

RU-09

Nizhny Novgorod, Russia

Location

RU-10

Novosibirsk, Russia

Location

RU-06

Petrozavodsk, Russia

Location

Ru-01, Ru-02, Ru-08, Ru-12, Ru-14

Saint Petersburg, Russia

Location

RU-07

Samara, Russia

Location

RU-13

Syktyvkar, Russia

Location

RU-05

Yekaterinburg, Russia

Location

KR-06

Busan, South Korea

Location

KR-05

Daegu, South Korea

Location

KR-04

Hwasun, South Korea

Location

Kr-01, Kr-02, Kr-03

Seoul, South Korea

Location

ES11

Badalona, Spain

Location

Es02, Es13, Es14

Barcelona, Spain

Location

Es01, Es04, Es09

Madrid, Spain

Location

ES-15

Málaga, Spain

Location

Es07, Es12

Pamplona, Spain

Location

ES10

Salamanca, Spain

Location

ES03

Santa Cruz de Tenerife, Spain

Location

ES08

Seville, Spain

Location

Es05, Es06

Valencia, Spain

Location

TW-02

Chiayi City, Taiwan

Location

Tw-04, Tw-07

Kaohsiung City, Taiwan

Location

TW-03

Taichung, Taiwan

Location

TW-05

Tainan, Taiwan

Location

Tw-01, Tw-06

Taipei, Taiwan

Location

GB03

Liverpool, United Kingdom

Location

GB01

Manchester, United Kingdom

Location

GB02

Milton Keynes, United Kingdom

Location

GB04

Southampton, United Kingdom

Location

Related Publications (4)

• Acs K, Miettinen JJ, Sergeev P, Heckel T, Diao Y, Witt-Mulder K, Thureson M, Bischler T, Huppunen ME, Suvela M, Obermuller J, Munawar U, Slipicevic A, Bargou RC, Lehmann F, Gelius SS, Norin S, Schjesvold F, Sonneveld P, Stuhmer T, Heckman CA. Efficacy of melflufen in multiple myeloma with mutated or deleted TP53. Exp Hematol Oncol. 2025 Dec 23;14(1):138. doi: 10.1186/s40164-025-00729-1.

  PMID: 41437395 DERIVED

• Schjesvold FH, Ludwig H, Delimpasi S, Robak P, Coriu D, Tomczak W, Pour L, Spicka I, Dimopoulos MA, Masszi T, Chernova NG, Sandberg A, Thuresson M, Norin S, Bakker NA, Mateos MV, Richardson PG, Sonneveld P. Health-related quality of life in relapsed/refractory multiple myeloma treated with melflufen and dexamethasone: analyses from the phase III OCEAN study. Haematologica. 2024 Jul 1;109(7):2331-2336. doi: 10.3324/haematol.2023.284635. No abstract available.

  PMID: 38426292 DERIVED

• Sonneveld P, Richardson PG, Ludwig H, Dimopoulos MA, Schjesvold FH, Hajek R, Abdulhaq H, Thuresson M, Norin S, Bakker NA, Mateos MV. Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):687-696. doi: 10.1016/j.clml.2023.05.004. Epub 2023 May 6.

  PMID: 37355418 DERIVED

• Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, Pour L, Spicka I, Masszi T, Doronin V, Minarik J, Salogub G, Alekseeva Y, Lazzaro A, Maisnar V, Mikala G, Rosinol L, Liberati AM, Symeonidis A, Moody V, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Hajek R, Mateos MV, Richardson PG, Sonneveld P; OCEAN (OP-103) Investigators. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 2022 Feb;9(2):e98-e110. doi: 10.1016/S2352-3026(21)00381-1. Epub 2022 Jan 12.

  PMID: 35032434 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

melflufen; L-melphalanyl-p-L-fluorophenylalanine ethyl ester; pomalidomide; Dexamethasone; dexamethasone acetate; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Chief Operating Officer
• Organization: Oncopeptides AB

trials@oncopeptides.com

+46 8 615 20 40

Study Officials

• Pieter Sonneveld, Prof.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 12, 2017
• Study Start: June 12, 2017
• Primary Completion: February 3, 2021
• Study Completion: February 3, 2023
• Last Updated: January 30, 2024
• Results First Posted: July 27, 2022

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); GB (4); US (14); DK (1); IT (8); NL (1); CZ (5); NO (2); KR (4); BE (3); AU (2); TW (5); FR (10); PL (8); GR (3); IL (6); HU (4); LI (2); RO (2); RU (10)