NC318, a Siglec-15 antibody, shows early evidence of disease control in subjects with Siglec-15 positive advanced or metastatic solid tumors in Phase 1 & 2 studies

Elaine Shum1, Han Myint2, Jahangheer S. Shaik2, Qinjie Zhou2, Emilia A. Barbu2, Aaron Morawski2, Hasan Abukharma2, Linda N. Liu2, Megan Nelson2, Stephanie Zeidan2, Zachary Cusumano2, Eric Novik3, Daniel Lee3, Omid Hamid4, Anthony Tolcher5, Sol Langermann2, Martin Gutierrez6

1Perlmutter Cancer Center, NY; 2NextCure Inc., MD; 3Generable Inc., NY; 4Angeles Clinic and Research Institute, CA; 5NEXT Oncology, TX; 6Hackensack University Medical Center, NJ

DISCLOSURE

  • Elaine Shum
    1. Consulting: AstraZeneca, Boehringer Ingelheim, Genentech (Roche)
  • Omid Hamid
    1. Consulting/Advisory Boards: Aduro, Akeso, Amgen, Beigene, Bioatla, BMS, Genentech (Roche), GSK, Immunocore, Idera, Incyte, Janssen, Merck, NextCure, Novartis, Pfizer, Sanofi/Regeneron, Seattle Genetics, Tempus, Zelluna.
  1. Speaker Bureau: BMS, Novartis, Pfizer, Sanofi/Regeneron.
    1. Contracted Research (For Institution): Arcus, Aduro, Akeso, Amgen, Bioatla, BMS, CytomX, Exelixis, Genentech (Roche), GSK, Immunocore, Idera, Incyte, Iovance, Merck, Moderna, Merck-Serono, NextCure, Novartis, Pfizer, Sanofi/Regeneron, Seattle Genetics, Torque, Zelluna.
  • Employees of NextCure Inc.
    1. Han Myint, Jahangheer S. Shaik, Qinjie Zhou, Emilia A. Barbu, Aaron Morawski, Hasan Abukharma, Linda N. Liu, Megan Nelson, Stephanie Zeidan, Zachary Cusumano.
  • Employees of Generable Inc.
  1. Eric Novik, Daniel Lee.

INTRODUCTION

  • 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 the discrimination of self and non-self immune regulation1.
  • S15 is an immune suppressor upregulated on various cancer cells and tumor-infiltrating myeloid cells. Its expression is non-overlapping with PD-L1. S15 leads to immunosuppression in the tumor microenvironment (TME)2.
  • NC318 is a first-in-class humanized IgG1κ monoclonal antibody that blocks S15-mediated immune suppression, providing opportunities to overcome anti-PD-1/PD-L1 therapy resistant tumors.
  • Phase 1 data was previously presented3. Here we will update the combined data of Phase 1 (n=49) and Phase 2 (n=47) from NC318-01 study.

1Macauley et al., Nat Rev Immunol (2014). 2Wang et al., Nat Med (2019). 3Tolcher et al., SITC (2019).

NC318: MECHANISM OF ACTION

S15 is Immunosuppressive in the Tumor Microenvironment

NC318 Blocks Immunosuppressive Activity Induced by S15

S15S15

Tumor

M2

macrophage

cell

OR

Myeloid

cell

Distinct

Differentiation S15-induced

and survival

myeloid cells

Inactive

T cell

Increase in

inflammatory

cytokines

Immunosuppression

and tumor growth

S15

TumorM2

NC318 cell macrophage

OR

Myeloid cell

Decreases

inflammatory

cytokines

Differentiation

and survival

S15

NC318 Dead tumor

cell

Tumor

Promotes T cell killing proliferation &

restores function

NC318 PHASE 1 & 2 STUDY DESIGN

Key Inclusion Criteria

  • Men and women aged 18 or older
  • ECOG performance status 0 to 1
  • Refractory/intolerant to standard of care with no limit to the number of prior treatment regimens
  • Measurable disease per RECIST v1.1
  • Subjects with advanced or metastatic low PD-L1 (TPS <50%) expressing malignancies

Key Exclusion Criteria

  • Inadequate hematologic, renal and hepatic function
  • Active autoimmune disease
  • History of interstitial lung disease or active noninfectious pneumonitis
  • Active infection requiring systemic therapy

Phase 1 Dose Escalation

8 mg (n=4)

24 mg (n=4)

80 mg (n=10)

240 mg (n=12)

400 mg (n=11)

800 mg (n=4)

1600 mg (n=4)

Phase 2 Dose Expansion

400 mg (n=47)

Lung

Head & Neck

Breast Ovarian

Study Design

  • Phase 1: 3 + 3 Design
    1. Subjects dosed every 2 weeks
    1. 28-dayDLT period
    1. Safety expansion enrolled additional subjects for biopsies
  • Phase 2: Simon two-stage design
    1. Subjects dosed every 2 weeks at 400 mg
  1. Subjects with advanced or metastatic low PD-L1 (TPS <50%) expressing malignancies
  1. Screening and on treatment biopsies

Primary Endpoint

  • Safety and tolerability

Secondary Endpoints

  • Assessment of PK
  • Assessment of antitumor activity/efficacy

Exploratory Endpoints

  • Immunogenicity, defined as the occurrence of anti-drug antibodies (ADA) to NC318
  • Biomarker changes of NC318 in peripheral blood and tumor

tissue

Tumor assessments

  • RECIST v1.1 and modified RECIST v1.1

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NextCure Inc. published this content on 13 November 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 13 November 2021 19:19:01 UTC.