8017 Background: SAR3419 (huB4-DM4) is an antibody-drug conjugate composed of a humanized IgG1 monoclonal antibody, huB4, which specifically targets the CD19 antigen, conjugated through a disulfide link to the maytansinoid derivative DM4, a potent tubulin inhibitor. After binding to the CD19 antigen, SAR3419 undergoes internalization and intracellular release of DM4.
METHODS
In this phase I/II study SAR3419 was administered by intravenous infusion, weekly for 8 to 12 doses, to pts with relapsed/refractory B-cell NHL expressing CD19.
RESULTS
Forty-four pts were enrolled at 7 dose levels from 10 to 70 mg/m². Main histologies were follicular (18; 41%) and diffuse large B-cell (17; 39%). Median number of prior regimens was 3 (1-8) and 19 pts had received prior transplantation. Twenty-eight pts were enrolled in the dose escalation part. Of 6 pts at 70 mg/m², 1 pt had a protocol defined dose limiting toxicity of neutropenia and 2 pts had grade 2 significant toxicities with late onset: blurred vision associated with corneal deposits and left bundle branch block. The maximum tolerated dose (MTD) was defined at 55 mg/m². Of 22 pts at the MTD, 4 pts had related reversible grade 3-4 toxicities after 6-8 doses: optic neuropathy, paraesthesia, neutropenia and thrombocytopenia. Of 38 pts at doses of 20 mg/m² or higher, 12 (32%) pts achieved an objective response including 6 CR/CRu, with no obvious dose effect. Of 22 pts at the MTD (55 mg/m²), 8 (36%) had a response, including 3 CR/CRu. Of 9 pts evaluable for response duration (RD), 4 pts had a RD ranging from 6 to at least 12 months.
CONCLUSIONS
These results demonstrate evidence of clinical activity and manageable safety, without significant myelosuppression. A modified schedule (4 weekly doses of 55 mg/m² followed by every 2 weeks dosing) is under evaluation. Updated clinical and pharmacokinetic data will be presented.