MVT-5873 (HuMab-5B1) is a fully human, IgG1 antibody targeting sialyl Lewis A (sLea), an epitope present on CA19-9. MVT-5873 was discovered from lymphocytes from a breast cancer patient immunized with a sLea-KLH vaccine. CA19-9 is widely expressed in pancreatic and other gastrointestinal tract cancers, where it plays a key role in tumor adhesion and metastatic potential and is a recognized marker of an aggressive phenotype.

MVT-5873 binds with high affinity and exquisite specificity to the sLea antigen epitope in a glycan microarray panel. MVT-5873 selectively binds to CA19-9 expressed on human tumor cell lines and induces cytotoxicity through antibody dependent cell-mediated and complement-dependent mechanisms. MVT-5873 has activity as both a single agent and in combination with chemotherapy in murine xenograft models of human pancreatic, colon, and small cell lung cancers. MVT-5873 appears to potentiate the activity of paclitaxel and of gemcitabine/nab-paclitaxel in a dose-dependent fashion in DMS-79 and BxPC3 xenograft models, respectively.

A first-in-human clinical trial of MVT-5873 opened January 2016. The trial is a Phase 1, open label, multicenter, non-randomized, dose escalation/expansion trial of MVT-5873 as a single agent (Group A) and in combination with conventional nab-paclitaxel/gemcitabine (Group B). Dose escalation uses a standard 3+3 design followed by expansion at MTD in 10 subjects..

Primary endpoints include 1) single-agent and combination MTD, 2) determination of the safety profile, and 3) pharmacokinetics. Secondary endpoints include 1) response rate, and 2) duration of response. Exploratory endpoints include 1) development of anti-MVT-5873 antibodies, 2) relationships between circulating CA19-9 levels and tumor response, 3) relationships between tumor IHC expression and circulating levels of CA19-9, 4) relationships between circulating CA19-9 levels and MVT-5873 pharmacokinetics (PK).

Key inclusion criteria:

• Histologically confirmed, progressive, locally-advanced or metastatic pancreatic ductal adenocarcinoma or other CA19-9 positive malignancies

• Evaluable or measurable disease

• ECOG PS of 0 or 1

• Adequate hematologic, hepatic, and renal function

• Measurable disease

• Serum CA19-9 levels ? 37 U/mL or CA19-9 positive tumor by IHC

Key exclusion criteria:

• Brain metastases unless treated and well controlled for at least 3 months

• Other active cancer likely to require treatment in the next 2 years

• Fewer than 28 days from prior anticancer therapy except for ongoing hormonal therapy administered for control of prostate cancer

• Significant cardiovascular risk

The results will be summarized with descriptive statistics. PK of MVT-5873 will be evaluated using non-compartmental methods.

Citation Format: Eileen M. O’Reilly, Todd M. Bauer, Jeffrey Infante, John C. Gutheil, Pamela Klein, Kenneth H. Yu, Maeve A. Lowery, Phil Livingston, Pricilla Martin, Wolfgang Scholz, Paul W. Maffuid. Phase I trial of HuMab-5B1 (MVT-5873), a novel monoclonal antibody targeting sLea, in patients with advanced pancreatic cancer and other CA19-9 positive malignancies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT026.