Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Melphalan

Bortezomib

Daratumumab

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with bortezomib at 1.3mg/m² S.Q. on Days 1, 4, 8, 11 and dexamethasone 20 mg (12 mg ≥ 75 years) Days 1, 4, 8, 11 and 40 mg (20 mg ≥ 75 years) on Day 15 and 22 of each 28-day cycle.

Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with daratumumab 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Dexamethasone p.o. 40 mg weekly (20 mg weekly for patients age ≥ 75 years).

Melphalan flufenamide (Melflufen)

This is an open-label Phase 1/2a study which will enroll patients that have relapsed or relapsed-refractory multiple myeloma to combination regimens of melflufen with currently approved agents. Patients will receive either melflufen+dexamethasone+bortezomib or melflufen+dexamethasone+daratumumab.

Study of Melphalan Flufenamide (Melflufen) + Dex With Bortezomib or Daratumumab in Patients With RRMM

An Open-Label Phase 1/2a Study of the Safety and Efficacy of Melflufen and Dexamethasone in Combination With Either Bortezomib or Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma

Toxicity was graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events Version 4.03.

DLT criteria that apply to Regimens A and B:

* Grade 3 non-hematologic toxicity preventing the administration of \> 1 dose of bortezomib or daratumumab during the 1st cycle.
* Grade 4 or greater non-hematologic toxicity.
* Grade 4 thrombocytopenia (platelet count \< 25,000 cells/ mm\^3) preventing the administration of \> 1 dose of bortezomib or daratumumab during the 1st cycle or with clinically significant bleeding during the 1st cycle.
* Grade 4 neutropenia (ANC \< 500 cells/mm\^3), lasting more than 7 days during the 1st cycle.
* Greater than 14 days' delay to meet the criteria for the start of a new cycle (Cycle 2) due to toxicity.

ORR was defined as the percentage of participants who achieved a best confirmed response of Partial Response (PR) or better.

BR defined by International Myeloma Working Group Uniform Response Criteria. BR= Complete Response (CR)/Stringent CR (sCR) defined as below negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow/plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence, Very Good Partial Response (VGPR)= serum and urine M-protein detectable by immunofixation but not on electrophoresis or \> 90% reduction in serum M-protein plus urine M-protein level \< 100 mg/24 hours, Partial Response (PR)= a \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \> 90% or to \< 200 mg/24 hours, Minimal Response (MR), Stable Disease (SD)= not meeting the criteria for other response options, Progressive Disease (PD)= increase of \> 25% from lowest response value in serum/urine M-component or bone marrow plasma cell percentage, or non-evaluable.

DOR is defined for participants with confirmed objective response (PR or better, which includes PR, VGPR, CR and sCR) as the time from the first documentation of objective response to the first documentation of objective progression or to death due to any cause, whichever occurs first.

Time from Cycle 1 Day 1 to a response of PR or better.

PFS was defined as the time in months from date of initiation of therapy to the earlier of confirmed disease progression or death due to any cause.

Time from the first dose of melflufen to death due to any cause.

DOCB was defined as time in months from the first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause.

TTP defined as time from first dose to first documented confirmed progression.

≥ Minimal response for participants included sCR, CR, VGPR, PR and MR.

Defined as time from date of initiation of therapy to start of next line of therapy.

TEAEs were defined as adverse events (AEs) that started after the first dose of study medication was administered and within 30 days of the last administration of the study treatment or before start of subsequent anticancer treatment (whichever occurred first) or that worsened after the first dose of study medication was administered.

Oncopeptides AB

All AEs that were spontaneously reported by the participant or detected during or between visits by non-directive questioning, through physical examination, laboratory test, or other assessments were reported in the eCRF. All participants included in the Safety Analysis Set were included in this analysis.

Participants were administered IV melflufen at a dose of 30 mg on Day 1 of each 28-day cycle in combination with SQ bortezomib at a dose of 1.3mg/m\^2 on Days 1, 4, 8, and 11 and dexamethasone PO at a dose of 20 mg (12 mg if the participants is ≥ 75 years of age) on Days 1, 4, 8, and 11 and 40 mg (20 mg if the participants is ≥ 75 years of age) on Day 15 and 22 of each 28-day cycle.

A (Melflufen+Bortezomib+Dex) 30 mg

Participants were administered IV melflufen at a dose of 40 mg on Day 1 of each 28-day cycle in combination with SQ bortezomib at a dose of 1.3mg/m\^2 on Days 1, 4, 8, and 11 and dexamethasone PO at a dose of 20 mg (12 mg if the participants is ≥ 75 years of age) on Days 1, 4, 8, and 11 and 40 mg (20 mg if the participants is ≥ 75 years of age) on Day 15 and 22 of each 28-day cycle.

A (Melflufen+Bortezomib+Dex) 40 mg

Participants were administered IV melflufen at a dose of 30 mg on Day 1 of each 28-day cycle in combination with daratumumab at a dose of 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Participants were also administered dexamethasone PO at a dose of 40 mg weekly (20 mg weekly if the participants is ≥ 75 years of age).

B (Melflufen+Daratumumab+Dex) 30 mg

Participants were administered IV melflufen at a dose of 40 mg on Day 1 of each 28-day cycle in combination with daratumumab at a dose of 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Participants were also administered dexamethasone PO at a dose of 40 mg weekly (20 mg weekly if the participants is ≥ 75 years of age).

B (Melflufen+Daratumumab+Dex) 40 mg

Regimen A - Melflufen 30mg + Bortezomib + Dexamethasone

Regimen A - Melflufen 40mg + Bortezomib + Dexamethasone

Participants were administered IV melflufen at a dose of 30 mg on Day 1 of each 28-day cycle in combination with IV daratumumab at a dose of 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Participants were also administered dexamethasone orally (PO) at a dose of 40 mg weekly (20 mg weekly if the participants is ≥ 75 years of age).

Regimen B - Melflufen 30mg + Daratumumab + Dexamethasone

Participants were administered IV melflufen at a dose of 40 mg on Day 1 of each 28-day cycle in combination with IV daratumumab at a dose of 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Participants were also administered dexamethasone orally (PO) at a dose of 40 mg weekly (20 mg weekly if the participants is ≥ 75 years of age).

Regimen B - Melflufen 40mg + Daratumumab + Dexamethasone

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Participants included in the Safety Analysis Set were included in the Baseline Characteristics. The Safety Analysis Set includes all patients that have received at least 1 dose (or partial dose) of melflufen, dexamethasone, or partner therapy (bortezomib or daratumumab).

On 04 November 2021, the study was terminated early during Phase 2a.

VP Chief Operating Officer

Only participants included in the DLT Analysis set were included in this analysis. The DLT Analysis Set was defined as all participants in Phase 1 that complete Cycle 1 of therapy or are discontinued due to a DLT event.

Phase 1: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)

All participants included in the Safety Analysis Set were included in this analysis.

Phase 2: Overall Response Rate (ORR)

VGPR

Non-evaluable

Missing

Best Response (BR)

Only participants included in the Safety Analysis Set who achieved a response of PR or better were included in this analysis.

Duration of Response (DOR)

Time to Response (TTR)

Progression-Free Survival (PFS)

Only participants included in the Safety Analysis Set were included in this analysis.

Overall Survival (OS)

All participants included in the Safety Analysis Set with a confirmed MR or better were included in this analysis.

Duration of Clinical Benefit (DOCB)

All participants in the Safety Analysis Set are included in this analysis.

Time to Progression (TTP)

Clinical Benefit Rate (≥ Minimal Response)

Time to Next Treatment (TTNT)

Any TEAEs

Any Grade 3 or Higher TEAEs

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

Participants were administered intravenous (IV) melflufen at a dose of 30 mg on Day 1 of each 28-day cycle in combination with subcutaneous (SQ) bortezomib at a dose of 1.3mg/m\^2 on Days 1, 4, 8, and 11 and dexamethasone orally (PO) at a dose of 20 mg (12 mg if the participants is ≥ 75 years of age) on Days 1, 4, 8, and 11 and 40 mg (20 mg if the participants is ≥ 75 years of age) on Day 15 and 22 of each 28-day cycle.

Participants were administered intravenous (IV) melflufen at a dose of 40 mg on Day 1 of each 28-day cycle in combination with subcutaneous (SQ) bortezomib at a dose of 1.3mg/m\^2 on Days 1, 4, 8, and 11 and dexamethasone orally (PO) at a dose of 20 mg (12 mg if the participants is ≥ 75 years of age) on Days 1, 4, 8, and 11 and 40 mg (20 mg if the participants is ≥ 75 years of age) on Day 15 and 22 of each 28-day cycle.

Participants were administered intravenous (IV) melflufen at a dose of 30 mg on Day 1 of each 28-day cycle in combination with IV daratumumab at a dose of 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Participants were also administered dexamethasone orally (PO) at a dose of 40 mg weekly (20 mg weekly if the participants is ≥ 75 years of age).

Participants were administered intravenous (IV) melflufen at a dose of 40 mg on Day 1 of each 28-day cycle in combination with IV daratumumab at a dose of 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Participants were also administered dexamethasone orally (PO) at a dose of 40 mg weekly (20 mg weekly if the participants is ≥ 75 years of age).

Overall Study

Antibodies

Antibodies, Monoclonal

Pomalidomide

Immunoglobulins

Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (20 mg for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.

IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.

Johan Harmenberg, MD, PhD

This study will evaluate melflufen in combination with dexamethasone in adult patients with relapsed or refractory multiple myeloma in whose disease is refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. All patients in the study will be treated with melflufen on Day 1 and dexamethasone on Days 1, 8, 15 and 22 of each 28-day cycle.

Melphalan flufenamide (melflufen) is a peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Peptidases are expressed in several cancers, including solid tumors and hematologic malignancies. Melphalan flufenamide is rapidly taken up by myeloma cells due to its high lipophilicity. Once inside the myeloma cell, the activity of melphalan flufenamide is determined by its immediate cleavage by peptidases into hydrophilic alkylator payloads that are entrapped. Melphalan flufenamide is 50-fold more potent than melphalan in myeloma cells in vitro due to increased intracellular alkylator concentration. It rapidly induces irreversible DNA damage leading to apoptosis of myeloma cells. Melphalan flufenamide displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, in vitro. Melphalan flufenamide also has demonstrated inhibition of angiogenesis and DNA damage with a lack of functional DNA repair in preclinical studies.

A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

A Single Arm, Open-Label, Phase 2 Study of Melflufen in Combination With Dexamethasone in Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Pomalidomide and/or an Anti-CD38 Monoclonal Antibody

The overall response rate (ORR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, or PR as their best response as assessed by the investigator. Response assessed by IMWG (International myeloma working group) criteria sCR-stringent complete response: CR plus Normal FLC (free light chain) ratio and absence of clonal cells in BM CR-complete response: Negative immunofixation in serum/urine; Disappearance of soft tissue plasmacytomas; \<5% plasma cells in BM; If only FLC disease, normal FLC ratio (0.26-1.65) VGPR-very good partial response: Serum/urine M-protein detectable by immunofixation but not electrophoresis or ≥90% reduction in serum M-protein and urine M-protein \<100 mg/24 h; If only FLC disease, \>90% decrease in the difference between involved and uninvolved FLC levels PR-partial response: 50% reduction of serum M-protein and soft tissue plasmacytomas, ≥90% reduction in urinary M-protein or to \<200 mg/24 h; other special cases if M-protein unmeasurable

Time from start of treatment to either progression or death, whichever comes first as assessed by the investigator using IMWG criteria. Progression of disease is defined by an increase of 25% from the lowest response for either of Serum M-component (absolute increase of ≥ 0.5 g/dL) or Urine M-component (absolute increase of ≥200 mg/ 24h); In patients without measurable M-protein a 25% increase in the difference between involved and uninvolved FLC (free light chain) levels (absolute increase must be \>10 mg/dL); If unmeasurable FLC levels, a 25% increase in bone marrow plasma cell percentage (absolute percentage must be \>10%); New bone or soft tissue plasmacytomas or definite increase in existing ones; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder

Time from first response to progression based on investigator assessment. See definitions of response and progression in ORR and PFS outcomes.

Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales, 1 Global Health Status scale, 3 symptom scales, and 6 single items. The recall period is 1 week (the past week). The scales are transformed to a 0 (worst) to 100 (best) scale. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better HRQoL. If at least 50% of the items from the scale had been answered, the missing items were assumed to have values equal to the average of those items which were present for that respondent.

Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L. The EQ-5D-3L questionnaire converts 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression of patient-reported, current-day health status into a "health utility" score. For the EQ-5D-3L questionnaire, each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. The EQ VAS scores rates "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). No imputation of missing items or composite scores were done. The scores for the 5 dimensions are used to compute a single utility score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual.

The clinical benefit rate (CBR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, PR, or MR as their best response as assessed by the investigator. See Primary Outcome (ORR) for definitions of response categories.

Duration from start of treatment to the first occurrence of a confirmed response of PR or better as assessed by the investigator. See definitions of response in Primary Outcome (ORR).

Duration from start of treatment to first evidence of disease progression as assessed by the investigator. See definitions of response and progression in ORR and PFS outcomes.

Precision For Medicine

The Safety Analysis Set for evaluation of adverse events included all patients who received at least one dose of melflufen or dexamethasone in the study. Patients that were triple-class refractory and those with extramedullary disease were defined as a subgroups of interest for evaluation.

Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.

Melphalan flufenamide (Melflufen)

Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.

Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set

Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass.

Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease

Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody.

Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease

Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.

Melphalan flufenamide (Melflufen)

Dexamethasone

Melphalan Flufenamide (Melflufen) + Dexamethasone

Age, Categorical

United States

Italy

France

Spain

Region of Enrollment

ECOG Performance Status Categories Status 0: Normal activity, fully active, able to carry on all pre-disease performance without restriction.

Status 1: Symptoms, but fully ambulatory, restricted in physically strenuous but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).

Status 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.

Status 3: Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours.

ECOG Performance Status

Baseline weight not recorded for one patient

Weight

International Staging System (ISS) is an assessment of risk factors for multiple myeloma ISS Stage I: Serum B2-microglobulin \< 3.5 mg/L, serum albumin ≥ 3.5 g/dL ISS Stage II: Not ISS Stage I or III ISS Stage III: Serum B 2-microglobulin ≥ 5.5 mg/L

International Staging System (ISS)

Time since initial diagnosis

Extramedullary disease at study entry

SPEP and UPEP

SPEP only

UPEP only

sFLC only

Unable to determine

Serum M-protein ≥ 0.5 g/dL (SPEP), urine M-protein ≥ 200 mg/24 hours (UPEP), or serum free light chain (sFLC) assay with FLC ≥ 10 mg/dL (≥ 100 mg/L) and abnormal serum immunoglobulin kappa to lambda FLC ratio.

5 patients did not have all assessments completed to adequately categorize

Type of measurable disease at baseline

High-risk cytogenetic abnormalities at study entry is defined as patients who had the genetic subtype t(4; 14), t(14:16), deletion 17p, gain 1q (+1q), or t(14,20) determined by Baseline fluorescence in situ hybridization (FISH)

Cytogenetic risk group based on FISH at study entry

Heavy-light chain combination at study entry

Global Clinical Project Lead

Full analysis set

Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.

Melphalan flufenamide (Melflufen)

Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.

Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass

Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody

Overall Response Rate (ORR)

Progression Free Survival (PFS)

Patients with a best response of PR or better as determined by the investigator.

Duration of Response

Overall Survival

Baseline value

Cycle 2 Day 1 Change from baseline

Cycle 4 Day 1 Change from baseline

Cycle 6 Day 1 Change from baseline

Cycle 8 Day 1 Change from baseline

This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease.

62 pts in the FAS included after QoL was added in Amd 4, whereof 48 pts in the sub-group of pts with TCR disease.

This outcome measure was not analyzed/reported separately for the sub-group of patients with EMD as there were limited no. of pts with EMD among the QoL patients. No data/results are available to report for patients with EMD.

Functional Status and Well-being: EORTC QLQ-C30

End of Treatment Change from baseline

Functional Status and Well-being: EQ-5D-3L

Clinical Benefit Rate

This outcome measure was pre-specified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and "Mel + Dex: Patients With TCR Disease.

This outcome measure was analyzed/reported for patients with a best response of PR or better in the full analysis set as well as in the sub-group of patients with triple class refractory disease.

This outcome measure was not analyzed/reported separately for the sub-group of patients with Extramedullary Disease. No data available to report for EMD patients.

Time to Response

This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease.

This outcome measure was analyzed/reported for patients in the full analysis set as well as in the sub-group of patients with triple class refractory disease.

This outcome measure was not analyzed/reported separately for the sub-group of patients with Extramedullary Disease. No data available to report for EMD patients.

Time to Progression

Lenalidomide

Angiogenesis Inhibitors

Growth Inhibitors

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.

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.

Melflufen

Pieter Sonneveld, Prof.

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.

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 were randomized to either one of two arms:

Arm A: Melphalan flufenamide (Melflufen) 40 mg on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.

Arm B: Pomalidomide 4 mg daily on Days 1 to 21 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.

Patients ≥ 75 years of age received a reduced dose of dexamethasone of 20 mg on Days 1, 8, 15 and 22 for both Arm A and Arm B.

Patients were to receive treatment until such time as there was documented disease progression, unacceptable toxicity, or the patient/treating physician determined it was not in the patient's best interest to continue.

Dose modifications and delays in therapy may have been implemented based on patient tolerability as detailed in the protocol. In the event of a cycle delay, unrelated to dexamethasone toxicity, it was recommended to continue dexamethasone weekly.

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

A Randomized, Controlled, Open-label, Phase 3 Study of Melflufen/Dexamethasone Compared With Pomalidomide/Dexamethasone for Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Lenalidomide

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.

ORR defined as the proportion of patients for whom the best overall confirmed response is stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by IRC.

DOR defined as the duration in months from first documentation of a confirmed response to first evidence of confirmed disease progression or death due to any cause.

OS defined as the time in months from randomization to date of death due to any cause. Patients who were still alive at end of study, or lost to follow up, were censored at the last day the patient was known to be alive.

Number of patients with TEAEs, including clinical laboratory and vital signs abnormalities, as assessed by CTCAE v4.0 are presented. No formal statistical analysis was performed for safety endpoints.

All-cause mortality is reported for the Full Analysis Set (all randomized patients; Arm A=246 patients, Arm B=249 patients). Adverse Events are reported for the Safety Analysis Set (all patients who received at least one or partial dose of melflufen, pomalidomide, or dexamethasone; Arm A=228 patients, Arm B=246 patients). Non-serious AEs were not calculated in this study. Data reported in the "Other Adverse Events" section include all TEAEs (non-serious AEs and serious AEs).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Melphalan Flufenamide (Melflufen) + Dex With Bortezomib or Daratumumab in Patients With RRMM	NCT03481556	Multiple Myelom...	Melphalan flufe... Dexamethasone Bortezomib Daratumumab	18 Years -	Oncopeptides AB
A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma	NCT02963493	Multiple Myelom...	Melphalan flufe... Dexamethasone	18 Years -	Oncopeptides AB
A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide	NCT03151811	Multiple Myelom...	Melflufen Pomalidomide Dexamethasone	18 Years -	Oncopeptides AB
A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma	NCT02963493	Multiple Myelom...	Melphalan flufe... Dexamethasone	18 Years -	Oncopeptides AB
A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide	NCT03151811	Multiple Myelom...	Melflufen Pomalidomide Dexamethasone	18 Years -	Oncopeptides AB

Spots Global Cancer Trial Database for melphalan flufenamide (melflufen)