Fdg-pet evaluation of ewing's sarcoma sensitivity

Abstract

This invention relates to methods for evaluating the efficacy of an IGF1R inhibitor, such as an anti-IGF1R antibody, for the treatment of an Ewing's sarcoma tumor by determining the level of tumoral glucose metabolism. Tumoral glucose metabolism is determining at an early point in the treatment regimen by any of several methods known in the art including FDG-PET/CT scan.

1 . A method for treating a Ewing's sarcoma tumor, in a subject, comprising evaluating glucose metabolism of the tumor after the subject has received a first dose of IGF1R inhibitor, but before a second dose of the inhibitor; or within 14 days of a first dose of IGF1R inhibitor but before a second dose of said inhibitor;
 wherein treatment with the IGF1R inhibitor is discontinued if glucose metabolism does not significantly decrease or remain constant after said first dose;   and continuing treatment with the IGF1R inhibitor if glucose metabolism does significantly decrease or remain constant after said first dose.   
     
     
         2 . The method of  claim 1  wherein glucose metabolism is evaluated by administering labeled glucose and monitoring its metabolism by the tumor. 
     
     
         3 . The method of  claim 2  wherein glucose metabolism is evaluated by  18 F-fluorodeoxyglucose positron emission tomography. 
     
     
         4 . The method of  claim 1  wherein the Ewing's sarcoma is recurrent or relapsed Ewing's sarcoma. 
     
     
         5 . The method of  claim 1  wherein the subject is a human. 
     
     
         6 . The method of  claim 1  comprising continuing treatment with the IGF1R inhibitor if glucose metabolism decreases by about 15% to about 25% after said first dose. 
     
     
         7 . The method of  claim 1  wherein the IGF1R inhibitor is an isolated antibody or antigen-binding fragment thereof. 
     
     
         8 . The method of  claim 7  wherein the IGF1R inhibitor is an isolated antibody or antigen-binding fragment thereof which is dalotuzumab or comprises CDR-H1, CDR-H2 and CDR-H3 of the heavy chain immunoglobulin variable region whose amino acid sequence is set forth in SEQ ID NO: 10, 12, 13, 14, 15, 16, 17 or 18; and CDR-L1, CDR-L2 and CDR-L3 of the light chain immunoglobulin variable region whose amino acid sequence is set forth in SEQ ID NO: 2, 4, 6, 8, 19, 20, 21, 22, 23 or 24. 
     
     
         9 . The method of  claim 7  wherein the antibody or fragment heavy and/or light chain variable region is linked to an immunoglobulin constant domain. 
     
     
         10 . The method of  claim 9  wherein immunoglobulin constant domain is selected from the group consisting of: kappa light chain, lambda light chain, gamma-1 heavy chain, gamma-2 heavy chain, gamma-3 heavy chain and gamma-4 heavy chain. 
     
     
         11 . The method of  claim 1  wherein the subject is administered an IGF1R antibody at a dose of about 1 to about 20 mg/kg every two weeks. 
     
     
         12 . The method of  claim 12  wherein the subject is administered an IGF1R antibody at a dose of about 10 mg/kg every two weeks. 
     
     
         13 . The method of  claim 1  wherein the subject is further administered a further chemotherapeutic agent. 
     
     
         14 . The method of  claim 13  wherein the further chemotherapeutic agent is aprepitant. 
     
     
         15 . A method for evaluating the effect of an IGF1R inhibitor on a Ewing's sarcoma tumor, in a subject, comprising:
 evaluating glucose metabolism of the tumor after the subject has received a first dose of IGF1R inhibitor, but before a second dose of the inhibitor; or   within 14 days of a first dose of IGF1R inhibitor but before a second dose of said inhibitor;   wherein the inhibitor is determined not to exhibit sufficient efficacy against the tumor if glucose metabolism does not significantly decrease or remain constant after said first dose; and wherein the inhibitor is determined to exhibit sufficient efficacy if glucose metabolism does significantly decrease or remain constant after said first dose   
     
     
         16 . The method of  claim 15  further comprising, if the inhibitor exhibits sufficient efficacy, continuing treatment with the inhibitor; or, if the inhibitor does not exhibit sufficient efficacy, discontinuing treatment with the inhibitor or increasing the dose of the inhibitor administered to the subject. 
     
     
         17 . The method of  claim 15  wherein the IGF1R inhibitor is an isolated antibody or antigen-binding fragment thereof which is dalotuzumab or comprises CDR-H1, CDR-H2 and CDR-H3 of the heavy chain immunoglobulin variable region whose amino acid sequence is set forth in SEQ ID NO: 10, 12, 13, 14, 15, 16, 17 or 18; and/or CDR-L1, CDR-L2 and CDR-L3 of the light chain immunoglobulin variable region whose amino acid sequence is set forth in SEQ ID NO: 2, 4, 6, 8, 19, 20, 21, 22, 23 or 24. 
     
     
         18 . The method of  claim 15  wherein the subject is administered the inhibitor in association with a further chemotherapeutic agent. 
     
     
         19 . The method of  claim 15  wherein glucose metabolism is evaluated by administering labeled glucose and monitoring its metabolism by the tumor. 
     
     
         20 . The method of  claim 19  wherein glucose metabolism is evaluated by  18 F-fluorodeoxyglucose positron emission tomography.