Trial in progress: A phase I/II, open-label, dose-escalation, safety and tolerability study of NC318 in subjects with advanced or metastatic solid tumors.

Abstract

TPS3166 Background: Siglec-15 (S15) is a member of the Siglec family (Sialic acid-binding Immunoglobulin Lectins), a distinct subgroup of immunoglobulin (Ig) superfamily proteins involved in discriminating self from non-self-immune regulation (Macauley MS et al. 2014). Nonclinical models demonstrate S15 mediates suppression of T cell proliferation and negatively regulates T cell function. NC318 is a first-in-class monoclonal antibody that blocks S15-mediated immune suppression and prevents tumor growth by normalizing T cell function and restoring anti-tumor immunity in the tumor microenvironment (Wang J et al. 2019). The clinical hypothesis of this study is that NC318 targeting of S15 can improve anti-tumor immune response and provide benefit in multiple oncology indications. Methods: This is a multi-center, first in human, phase 1/2, open-label, non-randomized study to determine the safety and tolerability, define maximum tolerated dose and/or pharmacologically active dose, assess preliminary efficacy, and explore predictive and pharmacodynamic biomarkers of NC318 in subjects with advanced or metastatic solid tumors. Key eligibility criteria included measurable disease based on RECIST v1.1 and consent for collection of biopsies at screening and on treatment (optional for phase 1). Phase 1 used a 3+3 dose escalation design to determine the recommended phase 2 dose (RP2D) and schedule of NC318 while identifying drug related toxicities (DLTs). Phase 2 enrollment is limited to non-small cell lung, ovarian, head and neck, and triple negative breast cancer subjects with PD-L1 tumor proportion scores <50% (additional tumor types are being evaluated for inclusion). Ongoing exploratory analyses include the assessment of predictive biomarkers associated with treatment benefit, and pharmacodynamic markers associated with study drug activity (e.g. evaluation of tumor biopsies and peripheral markers of inflammation). Phase 1 enrollment began October 2018 and completed in August 2019. The RP2D was defined and the phase 2 opened to enrollment October 2019. Clinical trial information: NCT03665285 .