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Wednesday, 09/05/2018 9:50:11 PM

Wednesday, September 05, 2018 9:50:11 PM

Post# of 44
Abstract out for WCLC.....


P2.09-24 - MERS67 is a Novel anti-NaPi2b Antibody and Demonstrates Differential Expression Patterns in Lung Cancer Histologic Subtypes
16:45 - 18:00 | Presenting Author(s): Rebecca Mosher | Author(s): Hui Yu, Kim Ellison, Pamela Shaw, Rafal Dziadziuszko, Eric Hailman, Christopher J. Rivard, Fred R. Hirsch

Abstract
Background
NaPi2b is a sodium-dependent phosphate transporter expressed in lung, ovarian, and thyroid cancers. Prior studies have suggested an enrichment of expression in lung adenocarcinoma (ACA).

XMT-1536 is a NaPi2b targeting ADC (Antibody Drug Conjugate) comprised of a humanized antibody (XMT-1535) conjugated with 10-15 auristatin F-HPA (AF-HPA) payload molecules via the Dolaflexin platform. AF-HPA is capable of controlled bystander-effect killing, resulting in efficacy in models with heterogeneous antigen expression, and is metabolized intra-tumorally to an active non-permeable metabolite to enable greater systemic tolerability. Previously, we demonstrated pre-clinical activity of XMT-1536 in human primary xenograft models of non-small cell lung cancer (NSCLC).

MERS67 is a human-rabbit chimeric antibody derived from XMT-1535. MERS67 has been formatted for use as an immunohistochemical reagent by multiple methods and expression has been shown to correlate with response in an unselected series of primary ovarian cancer xenografts. (AACR-EORTC, 2017)

We evaluated MERS67 to see if it would preferentially stain lung adenocarcinoma (ACA), as has been demonstrated using other NaPi2b antibodies.

Method
An immunohistochemical assay for MERS67 was established on a Leica BondRx Instrument. The assay was performed on tissue microarrays (TMA), including NSCLC and small cell lung cancer (SCLC) cell line arrays, and a NSCLC human tumor array. Tumors in the NSCLC array had previously been classified based on morphologic features only. All arrays were scored based on the H-score method.

To characterize the primary tumors further, the tumor TMA was stained with TTF-1 and p40, markers of ACA and squamous cell carcinoma (SqCC), respectively. Results of this staining were compared to MERS67 staining patterns.

Result
H-Scores in the NSCLC cell line TMA ranged from 0-260, and from 0-100 in the SCLC TMA. Within the tissue microarray, 99 individual cases were evaluable. By morphologic classification 63 cases were SqCC, and 23 cases were ACA. Using an arbitrary cut point of H=50, there was a statistically significant difference in the number of NaPi2b positive ACA cases (19/23) vs SqCC (3/63). Among 43 cases where p40 and TTF-1 were evaluable and were in agreement with morphologic diagnosis, 7/7 cases of ACA were positive for NaPi2b, while 0/36 SqCC were positive.

Conclusion
MERS67 is an anti-NaPi2b antibody that frequently demonstrates immunoreactivity in lung ACA. MERS67 is a chimeric antibody related to XMT-1536, a proprietary anti-NaPi2b ADC. Target expression using MERS67 is being evaluated in an ongoing XMT-1536 Phase 1 clinical trial enrolling non-squamous NSCLC patients.

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