Methods of treating cancer using 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione
AssigneeCelgene Corporation
InventorsGeorge W. Muller, Peter H. Schafer, Hon-Wah Man, Ling-Hua Zhang, Anita Gandhi, Rajesh Chopra
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Abstract
Provided herein are methods of treating, preventing and/or managing cancers, which comprise administering to a patient 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof.
Claims62
A method of treating or managing cancer, comprising administering to a patient in need of such treatment or management a therapeutically effective amount of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, which has the following structure:
- or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof.
A method for treating or managing non-Hodgkin's lymphoma, comprising:
- (i) identifying a patient having non-Hodgkin's lymphoma sensitive to treatment with 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione;
- and
- (ii) administering to the patient a therapeutically effective amount of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione or a pharmaceutically acceptable salt, solvate or hydrate thereof.
A method for predicting tumor response to treatment in a non-Hodgkin's lymphoma patient, comprising:
- (i) obtaining a biological sample from the patient;
- (ii) measuring the level of NF-κB activity in the biological sample;
- and
- (iii) comparing the level of NF-κB activity in the biological sample to that of a biological sample of a non-activated B-cell lymphoma subtype;
- wherein an increased level of NF-κB activity relative to non-activated B-cell subtype lymphoma cells indicates a likelihood of an effective patient tumor response to 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione treatment.
A method of monitoring tumor response to treatment in a non-Hodgkin's lymphoma patient, comprising:
- (i) obtaining a biological sample from the patient;
- (ii) measuring the level of NF-κB activity in the biological sample;
- (iii) administering a therapeutically effective amount of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, or a salt, solvate or hydrate thereof to the patient;
- (iv) obtaining a second biological sample from the patient;
- (v) measuring the level of NF-κB activity in the second biological sample;
- and
- (vi) comparing the level of NF-κB activity in the first biological sample to that in the second biological sample;
- wherein a decreased level of NF-κB activity in the second biological sample relative to the first biological sample indicates a likelihood of an effective patient tumor response.
A method for monitoring patient compliance with a drug treatment protocol in a non-Hodgkin's lymphoma patient, comprising:
- (i) obtaining a biological sample from the patient;
- (ii) measuring the level of NF-κB activity in the biological sample;
- and
- (iii) comparing the level of NF-κB activity in the biological sample to a control untreated sample;
- wherein a decreased level of NF-κB activity in the biological sample relative to the control indicates patient compliance with the drug treatment protocol.
A method for predicting tumor response to treatment in a non-Hodgkin's lymphoma patient, comprising:
- (i) obtaining a biological sample from the patient;
- (ii) purifying protein or RNA from the sample;
- and
- (iii) identifying increased expression of a gene associated with the activated B-cell phenotype of non-Hodgkin's lymphoma relative to control non-activated B-cell phenotype of non-Hodgkin's lymphoma;
- wherein increased expression of a gene associated with the activated B-cell phenotype of non-Hodgkin's lymphoma indicates a likelihood of an effective patient tumor response to 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione treatment.
A kit for predicting tumor response to treatment with 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, or a salt, solvate or hydrate thereof, in a non-Hodgkin's lymphoma patient, comprising:
- (i) a solid support;
- and
- (ii) a means for detecting the expression of a biomarker of an activated B-cell phenotype of non-Hodgkin's lymphoma in a biological sample.
A method of selecting a group of cancer patients based on the level of CRBN expression, or the levels of DDB1, DDB2, IRF4 or NFκB expression within the cancer, for the purposes of predicting clinical response, monitoring clinical response, or monitoring patient compliance to dosing by 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof;
- wherein the cancer patients are selected from multiple myeloma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, melanoma and solid tumor patients.
A method of selecting a group of cancer patients responsive to treatment with 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof;
- based on the level of CRBN expression, or the levels of DDB1, DDB2, IRF4 or NFκB expression within the patient's T cells, B cells, or plasma cells, for the purposes of predicting clinical response, monitoring clinical response, or monitoring patient compliance to dosing by 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof.
Dependencies are inferred from the claim text.