558TiP - Phase I study of effector-function enhanced monoclonal antibody (mAb), SEA-TGT, in advanced malignancies

Document Type

Article

Publication Date

2021

Publication Title

ESMO Congress 2021:ePoster Display

Keywords

oregon; portland; chiles

Abstract

Background

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory domains (TIGIT) is an inhibitory checkpoint receptor expressed on T-cells. TIGIT blocks the binding of CD226 on T-cells to CD155 and CD112 ligands, limiting T-cell activation. Relief of TIGIT blockade may stimulate anti-tumor T-cell responses. SEA-TGT is an investigational, humanized, nonfucosylated mAb directed against TIGIT. SEA-TGT binds TIGIT and activating FcγRIIIa leading to relief of inhibitory checkpoint signals directed at T-cells, depletion of immunosuppressive T-regulatory cells, and amplification of naïve and memory T-cells. Preclinically, SEA-TGT antitumor responses were greater than with other TIGIT mAbs without effector-enhanced backbones.

Trial design

The safety and antitumor activity of SEA-TGT in ∼231 adults (≥18 years) will be evaluated in this phase 1, multicenter, open-label, dose-escalation/expansion study (NCT04254107). Patients (pts) with histologically or cytologically confirmed relapsed, refractory, or progressive metastatic solid tumors (non-small cell lung, head and neck squamous cell or gastric/gastroesophageal junction carcinomas; cutaneous melanoma; bladder, ovarian or triple-negative breast cancers) or selected Hodgkin’s and non-Hodgkin’s lymphoma will be enrolled. SEA-TGT will be administered on Day 1 of 21-day cycles. Part A will assess the safety and tolerability of SEA-TGT to determine the maximum tolerated dose and recommended dose. Part B will assess the safety and antitumor activity of the recommended dose in disease-specific expansion cohorts. Part C will assess SEA-TGT in combination with pembrolizumab. Laboratory abnormalities, adverse events, dose-limiting toxicities, and dose-level safety and activity are primary endpoints. Secondary endpoints are objective response (OR) rates, duration of OR, complete response, progression-free survival, overall survival, pharmacokinetics (PK), and anti-drug antibodies. Exploratory analysis will include pharmacodynamics (PD), PK/PD relationships, biomarkers, and resistance to SEA-TGT. This trial is recruiting in Europe and North America.

Clinical trial identification

NCT04254107

Clinical Institute

Cancer

Department

Earle A. Chiles Research Institute

Department

Oncology

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