Study of AVE1642 Anti-IGF1R Monoclonal Antibody in Patients With Advanced Multiple Myeloma
Study of AVE1642 Anti-IGF1R Monoclonal Antibody in Patients With Advanced Multiple Myeloma
Primary Objectives:

 Study Part 1: Determine the selected dose of AVE1642 administered every 3 weeks based on
 pharmacokinetic (PK) (Clearance of AVE1642), pharmacodynamic (PD) (insulin-like growth factor
 1 [IGF-1] serum level) parameters, and eventual dose limiting toxicities (DLTs) in patients
 with recurrent, refractory multiple myeloma (MM).

 Study Part 2: Assess the safety of the combination of the selected dose of AVE1642 with the
 recommended dose of Velcade®.

 Secondary Objectives :

 Study Part 1:

 -  To assess the safety profile: type, incidence and intensity of drug related adverse
 events (AEs)

 -  To assess the biological activity of AVE1642 (saturation of the receptors and
 down-regulation) on malignant plasma cells and on peripheral blood mononuclear cells
 (PBMC) and granulocytes

 -  To assess the biological activity of AVE1642 on the signalization pathway of the IGF-1
 system (phosphorylated akt [pAkt], phosphorylated erk [pErk]) on malignant plasma cells
 when technically possible

 -  To define PK profile of AVE1642, and its PD effects on serum IGF 1, GF 2 and IGFBP-3

 -  To assess clinical efficacy (complete response [CR], partial response [PR], minimal
 response [MR] and stabilization) based on the European group for Blood and Marrow
 Transplantation (EBMT) criteria, when possible

 -  To assess potential immunogenicity by detection of human antihumanized antibodies (HAHA)
 anti-AVE1642

 Study Part 2:

 -  To detect any PK or PD interaction between AVE1642 and Velcade®

 -  To assess clinical efficacy (CR, PR, MR, no change [NC]) according to EBMT criteria when
 appropriate

 -  To assess biological activity of AVE1642 in combination with Velcade® on malignant
 plasma cells collected from bone marrow aspirates: saturation and down-regulation of the
 insulin-like growth factor 1 receptor (IGF-1R) and activity on the signalization pathway
 of the IGF-1 system (pAkt, pErk) when feasible

 -  To detect immunogenicity reaction (HAHA)

 -  To characterize PK and PD profile of a low dose (0.5 mg/kg) of AVE1642 expected to be
 non biologically active
Inclusion Criteria:

 -  Multiple myeloma confirmed by bone marrow aspirate or biopsy

 -  Patient had to have relapsed and/or refractory multiple myeloma after at least 1
 standard therapy, and have demonstrated disease progression

 -  Previous exposure to Velcade was allowed, provided no DLTs of Grade 3 or above had
 been observed during previous treatment (for Part 2 of the study only)

 Exclusion Criteria:

 -  Prior therapy with any IGF-1 system targeting compound

 -  History of allogenic stem cell transplantation in case of concomitant
 immunosuppressive therapy within 6 months before study entry. Patients having
 undergone autologous stem cell transplantation(s) may have been included in the study

 -  History of organ transplant and any patient receiving long term systemic
 immunosuppressive therapy

 The above information is not intended to contain all considerations relevant to a patient's
 potential participation in a clinical trial.