Validation of an immunoassay to selectively quantify the naked antibody of a new Antibody Drug Conjugate – SAR566658 – for pharmacokinetic interpretation improvement

An antibody drug conjugate targeting a GSTA glycosite-signature epitope of mucin1 expressed by non-small cell lung cancer

“…The positivity of 16A mAb staining in breast cancer (90%) is higher than SAR566658, 30,31 which binds to a sialylated unknown MUC1 sequence in bladder, breast, ovary, pancreatic, head and neck cancers with positivity of 59%, 29-35%, 70%, 59%, and 17% respectively. For those cancer tissues negative by 16A mAb staining, other mAbs targeting PDTR or GVTS motifs are worthy of further investigation.…”

“…A phase I clinical trial for SAR566658 in patients with CA6-positive ovarian, pancreatic, and breast tumors has been completed. 30,31 SAR566658 is CA6 mAb conjugated to DM4, a maytansinoid derivative, by SPDB (N-succinimidyl-4-(2-pyridyldithio) butanoate) linker, a hindered disulfide bond stable linker which is stable in blood stream. Partial response was observed in breast, ovarian and lung cancers.…”

Hepatotoxicity with antibody maytansinoid conjugates: A review of preclinical and clinical findings

“…SAR566658 (Sanofi) (anti‐CA6‐[SPDB]‐DM4) is an immunoconjugate consisting of a humanized monoclonal antibody against the tumor‐associated sialoglycotope CA6 (huDS6) conjugated to the cytotoxic maytansinoid DM4, via the cleavable SPDB linker (Pascual, Verdier, Malette, Mnich, & Ozoux, ). Upon antibody/antigen binding and internalization, the immunoconjugate releases DM4, which results in the inhibition of cell division and cell growth of CA6‐expressing tumor cells.…”

Translational Model-Based Strategy to Guide the Choice of Clinical Doses for Antibody-Drug Conjugates

“…SAR566658 and SAR3419 are ADCs with the same construct as SAR408701, that is, with the same drug (DM4) and linker moieties but with different targets. SAR566658 is composed of a humanized IgG1 mAb (huDS6) specific for a tumor‐associated sialoglycotope on MUC1, CA6, detected in solid tumors such as pancreas, ovary, breast, bladder, head and neck, and lung cancers, amongst others .…”

“…The present study aimed to propose a model‐based approach to help to select a phase 1 dosing regimen for an ADC (SAR408701), leveraging the available data of 2 other ADCs of the same construct: SAR3419 and SAR566658. First, preclinical PK monkey data for the 2 ADCs, SAR566658 and SAR3419, were used to predict human PK, and then the predicted PK parameters were compared with the observed clinical PK data to establish an allometric scaling strategy. Second, a translational‐oriented population PK‐PD model was established to quantitatively express the relationship between SAR408701 plasma concentration and tumor volume in severe combined immunodeficient (SCID) mice bearing a colon patient‐derived xenograft (PDX).Third, using the previously established allometric scaling strategy and the concentration for tumor growth inhibition, SAR408701 human concentration–time profiles were projected to help to select the appropriate dosing schedule in the FIH study.…”