robatumumab + temozolomide + irinotecan

This is a combination therapy consisting of **robatumumab**, a fully human monoclonal antibody that binds to and inhibits insulin-like growth factor receptor-1 (**IGF-1R**), together with **temozolomide**, an oral alkylating agent, and **irinotecan**, a topoisomerase I inhibitor. Robatumumab was primarily developed for the treatment of sarcomas, targeting IGF-1R to inhibit tumor growth and proliferation, and showed activity in Ewing sarcoma and osteosarcoma in clinical studies[1][3][7]. Temozolomide and irinotecan, both small molecules, have demonstrated synergistic antitumor activity against relapsed or refractory **Ewing sarcoma**, commonly used together due to their non-overlapping toxicities and complementary mechanisms[2][4][6]. Clinical use of robatumumab in combination with temozolomide and irinotecan specifically has been investigated in early-phase trials for patients with relapsed or refractory Ewing sarcoma and related sarcomas. Robatumumab was generally well tolerated but had limited durable efficacy overall[1][3][7]. Irinotecan and temozolomide together are well tolerated and offer an established response rate for relapsed Ewing sarcoma[2][4][6].