Single agent HuMab-5B1 (MVT-5873), a monoclonal antibody targeting sLea, in patients with pancreatic cancer and other CA19-9 positive malignancies.

4110 Background: MVT-5873, a fully human IgG1 monoclonal antibody (mAb), targets sialyl Lewis A (sLe a ), an epitope on CA19-9. CA19-9 is expressed in pancreatic (PDAC) and other GI cancers, plays a role in tumor adhesion and metastasis, and is a marker of an aggressive tumor phenotype. MVT-5873 is active as a single agent and with chemotherapy in murine xenografts. Methods: MVT-5873 was given IV every other week (Group 1) or weekly (Group 2). Eligible patients had progressive, locally-advanced or metastatic PDAC or other CA19-9+ malignancy and ECOG PS ≤1. Dose escalation followed a 3+3 design with a 10 patient expansion at MTD. Endpoints include safety, MTD, pharmacokinetics (PK) and efficacy. Exploratory endpoints include changes in serum CA19-9 levels. Results: As of 2-Feb 2017, data are available from N = 25 in Groups 1 (N = 9) and 2 (N = 16) at doses ranging from 1 to 3 mg/kg. Dose limiting toxicities of transient grade 3 elevations in AST, ALT, and total bilirubin were encountered at 3 mg/kg in both groups. Liver function laboratory abnormalities typically emerged and resolved within a week of dosing without significant clinical sequelae. Of toxicities deemed possibly related, most were low grade and included GI toxicity (abdominal pain/cramps/diarrhea/nausea) and infusion reactions. Infusion reactions were mitigated by using pre-medications and decreasing the infusion rate. Initial PK data demonstrate initial (20 hours) and terminal (211 hours) half-lives, comparable to other mAbs. Stable disease of > 4 months was observed in 24% of patients. CA19-9 levels were measured pre- and post-dose with each treatment. Immediate reductions showed dose-dependent reductions of up to 97% from baseline at 3 mg/kg. Downward trends of CA19-9 with successive doses were seen, with 48% and 22% of patients exhibiting ≥50% and ≥90% reductions in CA19-9 levels, respectively. Conclusions: Single agent MVT-5873 appears safe and tolerable at biologically active doses. DLTs included reversible serologic liver toxicity. The safety profile, efficacy, and reductions in serum CA19-9 levels over time support further development of MVT-5873 in this indication both as a single agent and in combination. Clinical trial information: NCT02672917.