AVE1642 + bortezomib

Combination of **AVE1642**, a humanized monoclonal antibody targeting the insulin-like growth factor 1 receptor (IGF-1R), and **bortezomib**, a small molecule proteasome inhibitor (marketed as Velcade). **AVE1642** selectively inhibits IGF-1R signaling, blocking proliferation and survival pathways in multiple myeloma (MM) cells, especially in CD45-negative subtypes with aggressive cytogenetic translocations (t(4;14), t(14;16)). **Bortezomib** induces apoptosis in MM cells through inhibition of the 26S proteasome and subsequent upregulation of pro-apoptotic factors such as Noxa and caspase-3 activation. The combination of AVE1642 and bortezomib shows synergy, with increased induction of apoptosis compared to either agent alone, specifically in CD45-negative myeloma cells. AVE1642 is developed by Sanofi-Aventis and bortezomib by Millennium Pharmaceuticals (now part of Takeda). The combination has been investigated in phase I clinical studies for relapsed/refractory multiple myeloma[1][3][5].

Other names

AVE1642 + Velcadeanti-IGF-1R monoclonal antibody + bortezomib