Etigilimab is an antibody against TIGIT (T-cell immunoreceptor with Ig and ITIM domains). TIGIT is a next generation checkpoint receptor shown to block T-cell activation and the body’s natural anti-cancer immune response. Etigilimab is an IgG1 monoclonal antibody which binds to the human TIGIT receptor on immune cells with a goal of improving the activation and effectiveness of T-cell and NK cell anti-tumor activity. Mereo completed a Phase 1a dose escalation clinical trial with etigilimab in patients with advanced solid tumors and enrolled patients in a Phase 1b study in combination with nivolumab in selected tumor types.
23 patients were treated in the Phase 1a dose escalation study with doses up to 20 mg/kg Q2W. Tumor types included colorectal cancer, endometrial cancer, pancreatic cancer and other tumors. No dose limiting toxicities were observed. In the Phase 1b combination study, a total of ten patients, nine of whom had progressed on prior anti-PD-1/PD-L1 therapies were enrolled at doses of 3, 10, and 20 mg/kg. Eight patients were evaluable for tumor growth assessment, and all of these patients had progressed on PD-1/PD-L1 therapies with best responses including one patient with a partial response another with stable disease. These patients remained on study for up to 224 days. No dose limiting toxicities (DLTs) were observed and the most common related adverse events included fatigue, rash, and pruritis.
Mereo recently initiated ACTIVATE, a Phase 1b/2 basket combination study.
PUBLIC PRESENTATIONS OF DATA FROM OUR ANTI-TIGIT PROGRAM INCLUDE:
- Initial results from a phase 1a/b study of etigilimab (MPH-313), an anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody, in advanced solid tumors -SITC 2018
- Anti-TIGIT biomarker study: Inhibition of TIGIT induces loss of T regs from tumors and requires effector function for tumor growth inhibition - AACR 2018
- Pharmacodynamic biomarkers for anti-TIGIT treatment and prevalence of TIGIT expression in multiple solid tumor types - AACR 2017
- Anti-TIGIT induces T cell-mediated anti-tumor immune responses and combines with immune checkpoint inhibitors to enhance strong and long term anti-tumor immunity-AACR 2017
- Antibody against T cell Immunoreceptor with Ig and ITIM domains (TIGIT) Induces anti-Tumor Immune Response and Generates Long-Term Immune Memory - AACR 2017
- Interim biomarker analysis etigilimab MPH-313 anti-TIGIT antibody advanced solid tumors supports TIGIT associated MOA Keystone 2019
SCIENTIFIC PUBLICATIONS:
- Mereo’s Etigilimab antibody program featured in Nature Biotechnology review of TIGIT-targeting’s potential to be the next validated cancer checkpoint: Dolgin, E. Antibody engineers seek optimal drug targeting TIGIT checkpoint. Nat Biotechnol 38, 1007–1009 (2020)
- A Phase 1a/b Open‑Label, Dose‑Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors: Niharika B. Mettu et al, Clin Cancer Res Nov 2021 DOI: 10.1158/1078-0432.CCR-21-2780