Melphalan flufenamide
DRACPC ID DRACPC0108
Active Ingredients Melphalan flufenamide
Description A peptide-drug conjugate composed of a peptide conjugated, via an aminopeptidase-targeting linkage, to the alkylating agent melphalan, with potential antineoplastic and anti-angiogenic activities. Upon administration, the highly lipophilic melphalan flufenamide penetrates cell membranes and enters cells. In aminopeptidase-positive tumor cells, melphalan flufenamide is hydrolyzed by peptidases to release the hydrophilic alkylating agent melphalan. This results in the specific release and accumulation of melphalan in aminopeptidase-positive tumor cells. Melphalan alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages. This results in the inhibition of DNA and RNA synthesis and the induction of apoptosis, thereby inhibiting tumor cell proliferation. Peptidases are overexpressed by certain cancer cells. The administration of melphalan flufenamide allows for enhanced efficacy and reduced toxicity compared to melphalan.
Synonyms J-1; J1; L-melphalanyl-p-L-fluorophenylalanine Ethyl Ester; Melflufen; Prodrug J1; Ygalo
Type Small Molecule
Disease Relapsed/Refractory Multiple Myeloma (RRMM)
Classification
Peptide and derivative
Structure Information
Molecular Formula C24H30Cl2FN3O3
Molecular Weight 498.4
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name ethyl (2S)-2-[[(2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate
InChI InChI=1S/C24H30Cl2FN3O3/c1-2-33-24(32)22(16-18-3-7-19(27)8-4-18)29-23(31)21(28)15-17-5-9-20(10-6-17)30(13-11-25)14-12-26/h3-10,21-22H,2,11-16,28H2,1H3,(H,29,31)/t21-,22-/m0/s1
InChI_Key YQZNKYXGZSVEHI-VXKWHMMOSA-N
SMILES O=C(OCC)[C@@H](NC([C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1)=O)CC2=CC=C(F)C=C2
External Codes
PubChem CID 9935639
DrugBank Accession Number DB16627
NCI Thesaurus Code C107680
UNII F70C5K4786 GSRS
CAS 380449-51-4
Drug approval
Drug indication
Melphalan flufenamide is indicated in combination with dexamethasone to treat adults with relapsed or refractory multiple myeloma who have received ≥4 therapies and are refractory to at least one proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody. The FDA has withdrawn the drug from the market for this indication following phase 3 trial data showing decreased overall survival.
| Drug Name | Strength | Dosage Form/Route | Company | Marketing Status | Drug ID | Approval year |
|---|---|---|---|---|---|---|
| PEPAXTO | EQ 20MG BASE/VIAL | POWDER;INTRAVENOUS | ONCOPEPTIDES AB | Discontinued | NDA: 214383 | 2021 |
| Pepaxti | Depends on body weight | Infusion (drip) | Oncopeptides AB | Prescription | EMEA/H/C/005681 | 2022 |
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT04534322 | An Expanded Access Program Protocol for Melphalan Flufenamide in Combination With Dexamethasone in Patients With Triple Class Refractory Multiple Myeloma | Relapsed and/or Refractory Multiple Myeloma | Expanded Access Program (Approved for marketing) | Treatment |
| NCT03151811 | 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 | Multiple Myeloma | Phase 3 | Treatment |
| NCT03481556 | 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 | Multiple Myeloma | Phase 1/2 | Treatment |
| NCT03639610 | A Study of the Pharmacokinetics of Melphalan During Treatment With Melflufen and Dexamethasone in Patients With Relapsed Refractory Multiple Myeloma and Impaired Renal Function | Renal Impairment; Multiple Myeloma | Phase 2 | Treatment |
| NCT04649060 | 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 | Relapsed Multiple Myeloma; Relapsed-Refractory Multiple Myeloma | Phase 3 | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
