Study of Melphalan Flufenamide (Melflufen) in Combination With Daratumumab in Relapsed Refractory Multiple Myeloma
A Randomized, Controlled, Open-Label Phase 3 Study of Melflufen in Combination With Daratumumab Compared With Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma
Lead SponsorOncopeptides AB
Indication/ConditionRelapse Multiple Myeloma ...
Intervention/TreatmentMelphalan Flufenamide Dexamethasone Daratumumab
This is a randomized, controlled, open-label, Phase 3 multicenter study which will enroll patients that have Relapsed Refractory Multiple Myeloma and are double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or have received at least 3 prior lines of therapy including an IMiD and a PI.
Patients will receive treatment of melflufen+dexamethasone+daratumumab or daratumumab until documented progressive disease, unacceptable toxicity or patient/treating physician decision. Patients in the daratumumab treatment arm will after confirmed progressive disease have the option to receive treatment with melflufen+dexamethasone+daratumumab.
30 mg intravenous (i.v.) infusion
40 mg weekly (if ≥75 years 20 mg weekly). Oral tablets
1800 mg subcutaneous injection
Treatment will be given in cycles and may be given in an outpatient treatment setting. Each cycle is 28 days. Melflufen 30 mg i.v. infusion at Day 1 of each cycle Dexamethasone 40 mg p.o. weekly (if ≥75 years 20 mg weekly). Daratumumab 1800 mg s.c. Cycle 1 and 2: Day 1, 8, 15 and 22. Cycle 3 to 6: Day 1 and 15. Cycle 7+: Day 1.
Treatment will be given in cycles and may be given in an outpatient treatment setting. Each cycle is 28 days. • Daratumumab 1800 mg s.c. Cycle 1 and 2: Day 1, 8, 15 and 22. Cycle 3 to 6: Day 1 and 15. Cycle 7+: Day 1.
Inclusion Criteria: A prior diagnosis of multiple myeloma with documented disease progression after last line of therapy Double refractory to an immunomodulatory drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or have received at least 3 prior lines of therapy including an IMiD and a PI. Prior treatment with daratumumab or another anti-CD38 antibody may be allowed under certain circumstances Male and women of childbearing potential agrees to use contraception during the treatment period and during a specified time period after the last dose Exclusion criteria: Primary refractory disease (i.e. never responded with at least Minimal Response to any prior therapy for multiple myeloma) Prior treatment with CD38 CAR-T cell therapy or CD38/CD3 bispecific antibodies Any medical condition that may interfere with safety or participation in this study 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 Known or suspected amyloidosis, plasma cell leukemia or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) Known central nervous system (CNS) or meningeal involvement of myeloma Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation of therapy or prior allogeneic stem cell transplantation with active graft-versus-host-disease Prior treatment with melflufen