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).

Spots Global Cancer Trial Database for Study of Melphalan Flufenamide (Melflufen) + Dex With Bortezomib or Daratumumab in Patients With RRMM

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