Methods and compositions for treatment of cancer

Inventors

Maniar, Manoj • Raza, Azra • WILHELM, FRANCOIS

Assignees

Columbia University in the City of New York • Traws Pharma Inc

Abstract

The invention discloses a method of treating cancer refractory to an anticancer agent comprising administering to a cancer patient a pharmaceutical composition comprising at least one compound of Formula 1 Where R1 is selected from the group consisting of —NH2, —NH—CH2—COOH, —NH—CH(CH3)—COOH, —NH—C(CH3)2—COOH, —NH—CH2—CH2—OH and —N—(CH2CH2OH)2 or a pharmaceutically acceptable salt of such a compound, and an anticancer agent.

Core Innovation

The invention relates to anti-cancer compositions and methods for treating a patient suffering from refractory myelodysplastic syndromes (MDS) that is refractory to an erythropoiesis stimulating agent (ESA). The method comprises administering rigosertib represented by Formula 1 together with an ESA to the patient.

The disclosed approach addresses resistance to ESA by using rigosertib together with the ESA, where the combination overcomes resistance to the ESA. The combination further causes transfusion independence in the patient, including in refractory MDS contexts described as ESA-refractory.

The disclosure includes rigosertib as a non-ATP competitive multi-kinase inhibitor and identifies rigosertib/ON 01910.Na as targeting PLK1/PI3K pathways, thereby inducing G2-M arrest and apoptosis. It further describes rigosertib in relation to overcoming drug/ESA resistance and reports outcomes in refractory hematologic cancers, with particular attention to refractory MDS and transfusion independence signals.

Claims Coverage

The document contains one independent method claim directed to treating ESA-refractory refractory myelodysplastic syndromes (MDS) using a combination of rigosertib (Formula 1) and ESA. The core inventive feature is the combination treatment that overcomes ESA resistance and causes transfusion independence, with dependent claims adding timing, route/regimen, patient subgroups/outcomes, symptom sets, and quantitative pharmacokinetic targets.

Across the claim set, the core coverage is the administration of rigosertib (Formula 1) together with an ESA to treat ESA-refractory MDS, where the combination overcomes ESA resistance and causes transfusion independence. Dependent claim limitations further constrain the temporal relationship between rigosertib and ESA administration, add defined patient-risk context for transfusion independence, specify patient symptom/parameter sets, and include quantitative oral pharmacokinetic targets.

Stated Advantages

Documented Applications