Biomarkers for pre-selection of patients for anti-IGF1R therapy
View Patent ↗The present invention provides methods for identifying patients whose cancers are likely to be responsive to IGF1R inhibitory anti-cancer therapy along with methods for treating such patients. Patients identified by a method of the present invention can be treated with any of several known IGF1R inhibitory agents including antibodies, small molecule inhibitors and anti-sense nucleic acids.
1. A method for treating a non-small cell lung tumor, an ovarian tumor, a neuroblastoma tumor or an osteosarcoma tumor in a mammalian patient wherein growth or survival of the tumor is mediated by IGF1R expression or activity said method comprising:
(a) selecting a mammalian patient having a non-small cell lung tumor, an ovarian tumor, a neuroblastoma tumor or an osteosarcoma tumor expressing phosphorylated IRS-1 tyrosine 896 or phosphorylated IRS-1 tyrosine 612; and
(b) administering to said mammalian patient a therapeutically effective amount of an isolated antibody that binds specifically to IGF1R comprising a light chain immunoglobulin variable domain comprising the amino acid sequence: EIVLTQSPGT LSVSPGERATLSCRASQSIGSSLHWYQQKPGQAPRLLIKYASQSLSGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCHQSSRLPHTFGQGTKVEIKRT (amino acids 20-128 of SEQ ID NO: 8); and a heavy chain immunoglobulin variable domain comprising the amino acid sequence: EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSFAMHWVRQAPGKGLEWISVIDTRGATYYA DSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARLGNFYYGMDVWGQGTTVTVSS (amino acids 20-137 of SEQ ID NO: 10); wherein said antibody inhibits growth or survival of said tumor.
2. The method of claim 1 wherein the tumor is an osteosarcoma tumor.
3. The method of claim 2 wherein the antibody is a monoclonal antibody and the patient is a human.
4. The method of claim 2 wherein the antibody is a fully human monoclonal antibody and the patient is a human.
5. The method of claim 3 wherein said light chain immunoglobulin variable domain is conjugated to an immunoglobulin kappa constant domain and said heavy chain immunoglobulin variable domain is conjugated to an immunoglobulin gamma 1 constant domain.
6. The method of claim 4 wherein said light chain immunoglobulin variable domain is conjugated to an immunoglobulin kappa constant domain and said heavy chain immunoglobulin variable domain is conjugated to an immunoglobulin gamma 1 constant domain.
7. The method of claim 3 wherein said patient is administered the monoclonal antibody in association with one or more additional anti-cancer agents.
8. The method of claim 7 wherein the patient is administered said monoclonal antibody in association with one or more additional anti-cancer agents selected from the group consisting of: paclitaxel, thalidomide, docetaxel, gefitinib, temozolomide, lonafarnib, tipifarnib, letrozole, doxorubicin, cis-platin, oxaliplatin, camptothecin, topotecan, etoposide, vincristine, vinblastine, raloxifene, gemcitabine, retinoic acid, tamoxifen, trastuzumab, cetuximab and octreotide.
9. The method of claim 4 wherein said patient is administered the monoclonal antibody in association with one or more additional anti-cancer agents.
10. The method of claim 9 wherein the patient is administered said monoclonal antibody in association with one or more additional anti-cancer agents selected from the group consisting of: paclitaxel, thalidomide, docetaxel, gefitinib, temozolomide, lonafarnib, tipifarnib, letrozole, doxorubicin, cis-platin, oxaliplatin, camptothecin, topotecan, etoposide, vincristine, vinblastine, raloxifene, gemcitabine, retinoic acid, tamoxifen, trastuzumab, cetuximab and octreotide.
11. The method of claim 8 wherein the additional anti-cancer agent is paclitaxel.
12. The method of claim 8 wherein the additional anti-cancer agent is docetaxel.
13. The method of claim 8 wherein the additional anti-cancer agent is gefitinib.
14. The method of claim 8 wherein the additional anti-cancer agent is cis-platin.
15. The method of claim 8 wherein the additional anti-cancer agent is oxaliplatin.
16. The method of claim 8 wherein the additional anti-cancer agent is octreotide.