Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma

Summary

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with Relapsed-Refractory Multiple Myeloma (RRMM) who were either double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or had received at least 3 prior lines of therapy including an IMiD and a PI. Patients received treatment with melflufen+dexamethasone+daratumumab or daratumumab until documented progressive disease, unacceptable toxicity, or patient/treating physician decision. Patients in the daratumumab treatment arm had the option to receive treatment with melflufen+dexamethasone+daratumumab after confirmed progressive disease.

Timeline

Start

2020-12-21

Primary completion

2022-02-07

Completion

2022-02-07

Outcome

Met primary endpoint

Stopped (Business): “The sponsor decided to terminate the study due to financial issues following an FDA request for a partial clinical hold.”

registry analysis (superiority test); Arm A (Melflufen+Dexamethasone+Daratumumab) vs Arm B (Daratumumab); p =0.0032; Hazard Ratio (HR) 0.184 (95% CI 0.052 to 0.650); Log Rank NCT04649060 ↗

paper melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM PMID 37646660 ↗

Publications

• Pour L, Szarejko M, Bila J, Schjesvold FH, Spicka I, Maisnar V, Jurczyszyn A, Grudeva-Popova Z, Hajek R, Usenko G, Thuresson M, Norin S, Jarefors S, Bakker NA, Richardson PG, Mateos MV. Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study. Haematologica. 2024 Mar 1;109(3):895-905. doi: 10.3324/haematol.2023.283509.
• Ocio EM, Efebera YA, Hajek R, Straub J, Maisnar V, Eveillard JR, Karlin L, Mateos MV, Oriol A, Ribrag V, Richardson PG, Norin S, Obermuller J, Bakker NA, Pour L. ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study. Haematologica. 2024 Mar 1;109(3):867-876. doi: 10.3324/haematol.2023.283490.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Daratumumab	Monoclonal antibody	1800 mg	Subcutaneous
Subject	Dexamethasone	Small molecule	20 mg	Oral
Subject	Dexamethasone	Small molecule	40 mg	Oral
Subject	Melphalan flufenamide	Peptide	30 mg	Intravenous

Indications