Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cycledextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremsophor EL; Dimethyl sulfoxide; D-mannitol; Trebalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The invention provides compounds of formula (I), that are peptidase enhanced cytotoxics. The invention further provides pharmaceutical compositions comprising the compounds, and the use of the compounds or pharmaceutical compositions as a medicament, particularly for use in the treatment or prophylaxis of cancers such as multiple myeloma, osteosarcoma, breast cancer, lung cancer, ovarian cancer, leukaemia and lymphoma.

Abstract: The present invention relates to a particularly advantageous new therapeutic use of melflufen (melphalan flufenamide; L-melphalanyl-4-fluoro-L-phenylalanine ethyl ester), or a salt thereof: in the treatment or prophylaxis of multiple myeloma in a patient having multiple myeloma who:—has not received a stem cell transplant; or—has received a stem cell transplant that was at least 5 years ago; or—is 75 years old or older; or—has not received a stem cell transplant and is 75 years old or older, or has received a stem cell transplant that was at least 5 years ago and is 75 years old or older; or—has received a stem cell transplant and the disease subsequently progressed at least 36 months after the transplant. The inventors have found that melflufen, and in particular melflufen in combination with dexamethasone, is surprisingly effective for the treatment or prophylaxis of multiple myeloma in these patients.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The invention provides melflufen, or a salt thereof, or a pharmaceutical formulation comprising melflufen, or a salt thereof, for use in the treatment and/or prophylaxis of immunoglobulin light chain (AL) amyloidosis. The invention also provides dosage regimens and kits that find utility in the treatment and/or prophylaxis of AL amyloidosis, and methods for the treatment and/or prophylaxis of AL amyloidosis, and uses of melflufen, or a salt thereof, for the manufacture of a medicament for the treatment of AL amyloidosis.

Abstract: The invention provides a pharmaceutical formulation comprising (or consisting essentially of) the following components: i) melflufen, or a salt thereof; ii) propylene glycol; iii) optionally one or more physiologically acceptable aqueous solvent(s); and iv) optionally one or more additional therapeutic agent(s); or a pharmaceutical formulation comprising (or consisting essentially of) the following components: i) melflufen, or a salt thereof; ii) polyethylene glycol; iii) optionally one or more physiologically acceptable aqueous solvent(s); and iv) optionally one or more additional therapeutic agent(s). The invention also provides methods for preparing the pharmaceutical formulations of the invention, kits and uses of the pharmaceutical formulations of the invention.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention provides melflufen (melphalan flufenamide; L-Melphalanyl-4-fluoro-L-phenylalanine ethyl ester), or a salt thereof, for use in the treatment or prophylaxis of multiple myeloma, wherein a dosage of melflufen (excluding the mass of any salt) is administered as a parenteral dosage at an infusion rate of 1.0 to 1.8 mg/min. Also provided is melflufen, or a salt thereof, for use in the treatment or prophylaxis of a cancer, for example a solid cancer, wherein a dosage of melflufen is administered as a parenteral dosage at an infusion rate less than 0.8 mg/min (for example 0.3 to 1.0 mg/minor for example 0.3 to 0.8 mg/min).

Abstract: The invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof (Formula I), wherein, each R1—R30 is independently selected from the group consisting of H and deuterium, and at least one of R1—R30 is deuterium with an abundance level greater than the naturally occurring abundance of deuterium. The invention also provides pharmaceutical compositions containing the compounds, and uses of the compounds.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; diso dium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; ?-cyclodextrin; ocyclodextrin; hydroxypropyl-?-cyclodextrin; sulfobutylether-?-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.

Abstract: The present invention provides a process for the production of compound (III) or a deprotected product thereof: comprising reacting compound (II) with chloroacetic acid, in the presence of a reducing agent; wherein PG is a protecting group and R is OH in a suitably protected form or (A). The invention further provides intermediate compounds formed in the process of the invention, and processes for the production of intermediate compounds.

Abstract: The present invention is directed to lyophilized pharmaceutical preparations comprising melphalan flufenamide, or pharmaceutically acceptable salts thereof, and sucrose. Further independent claims are directed to methods for their preparation, compositions comprising the lyophilized pharmaceutical preparations and their use in the treatment of cancer.

Abstract: The present invention is directed to lyophilized pharmaceutical preparations comprising melphalan flufenamide, or pharmaceutically acceptable salts thereof, methods for their preparation, compositions comprising the lyophilized pharmaceutical preparations and their use in the treatment of cancer.