1074TiP SGNTGT-001: A phase I study of SGN-TGT, an effector-function enhanced monoclonal antibody (mAb), in advanced malignancies

Document Type

Article

Publication Date

9-2020

Publication Title

Annals of Oncology

Abstract

Background

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor expressed on subsets of T cells and NK cells. SGN-TGT is an effector-function enhanced human mAb that targets TIGIT with pico-molar affinity and blocks TIGIT’s interaction with CD155 and CD112. SGN-TGT was developed to have amplified binding to and engagement of Fcγ receptors. Enhanced effector function increases TIGIT+ T-regulatory cell depletion, enhances innate immune cell activation, and augments naïve and memory CD8+ T-cell responses. Preclinically, SGN-TGT elicits superior anti-tumor immune responses compared to other TIGIT mAbs without effector-enhanced backbones, with curative anti-tumor activity as monotherapy and in combination with other immune-modulators.

Trial design

This phase I, open-label, multicenter, dose-escalation study [NCT04254107] is assessing the safety and tolerability of SGN-TGT monotherapy in ∼85 adults (≥18 years) with histologically or cytologically confirmed relapsed, refractory, or progressive metastatic solid tumors (non-small cell lung or gastric carcinomas) or lymphomas (classical Hodgkin lymphoma, diffuse large B-cell lymphoma, or peripheral T-cell lymphoma, not otherwise specified). SGN-TGT will be infused on Day 1 of 21-day cycles. In Part A, the safety and tolerability of SGN-TGT will be assessed in ∼25 subjects to identify the maximum tolerated dose and recommended phase II dose (RP2D). In Part B, the safety and antitumor activity of the RP2D will be assessed in ∼60 subjects in disease-specific expansion cohorts. Primary endpoints are adverse events, laboratory abnormalities, dose-limiting toxicities, and dose-level safety and activity. Secondary endpoints are objective response (OR) rates, best response rates, duration of OR, complete response, progression-free survival, and overall survival, PK, and antidrug antibodies. Exploratory biomarkers of SGN-TGT-mediated PD effects, PK-PD correlations, and correlative analyses of PD measurements and response, toxicity, and resistance will be explored. The study was opened April 2020 and is enrolling.

Clinical trial identification

NCT04254107

Clinical Institute

Cancer

Department

Oncology

Department

Earle A. Chiles Research Institute

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