Abstract 1074TiP
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.
Editorial acknowledgement
Medical writing assistance was funded by Seattle Genetics, Inc., and provided by Charlotte Yap of MMS Holdings, Inc.
Legal entity responsible for the study
Seattle Genetics.
Funding
Seattle Genetics.
Disclosure
E. Garralda: Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: F. Hoffman/La Roche; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Neomed Therapeutics Inc; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Janssen Global Services; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: TFS; Advisory/Consultancy: Alkermes; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Thermo Fisher; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Meyer Squibb; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Travel/Accommodation/Expenses: Menarini; Travel/Accommodation/Expenses: Glycotope. R.E. Sanborn: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Panel expert; symposium presenter: AstraZeneca; Speaker Bureau/Expert testimony, Educational Presentation: Amgen; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Peregrine Pharmaceuticals; Advisory/Consultancy: ARAID/Takeda; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Celldex; Advisory/Consultancy: AbbVie; Research grant/Funding (self), Investigator-sponsored trial: Merck; Research grant/Funding (institution): BMS; Research grant/Funding (institution): MedImmune. A.R. Minchom: Honoraria (self): Bayer Pharmaceuticals; Honoraria (self): Novartis Oncology; Advisory/Consultancy: Janssen Pharmaceuticals; Advisory/Consultancy: Faron Pharmaceuticals; Advisory/Consultancy: Merck Pharmaceuticals; Travel/Accommodation/Expenses: LOXO Oncology. D. Davar: Advisory/Consultancy: Array; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Vedanta Biosciences; Speaker Bureau/Expert testimony: IC-ONC; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Checkmate Pharmaceuticals; Research grant/Funding (institution): GSK/Tesaro. G. Curigliano: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Ellipsis; Full/Part-time employment: University of Milano, Istituto Europeo di Oncologia, IRCCS, Milan Italy. V. Ribrag: Advisory/Consultancy, Research grant/Funding (institution): Epizyme; Research grant/Funding (institution): ArgenX; Advisory/Consultancy: Servier; Advisory/Consultancy: NanoString; Advisory/Consultancy: Gilead; Advisory/Consultancy: PharmaMar; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Roche; Advisory/Consultancy: Infinity; Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca Ab; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Forma Therapeutics; Research grant/Funding (institution): Gamamabs; Research grant/Funding (institution): H3 Biomedicine; Research grant/Funding (institution): Imcheck Therapeutics; Research grant/Funding (self), Research grant/Funding (institution): Janssen Cilag; Research grant/Funding (institution): Kyowa Kirin Pharm. Dev; Research grant/Funding (institution): Lilly France; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Nanobiotix; Research grant/Funding (institution): Octimet Oncology Nv; Research grant/Funding (self), Research grant/Funding (institution): Sanofi; Research grant/Funding (self), Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (self), Research grant/Funding (institution): Janssen; Research grant/Funding (self), Research grant/Funding (institution): Merck; Research grant/Funding (self), Research grant/Funding (institution): Novartis; Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): Aduro Biotech; Research grant/Funding (institution): Agios Pharmaceuticals; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Arno Therapeutics; Research grant/Funding (institution): Astex Pharmaceuticals; Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Basilea Pharmaceutica International Ltd; Research grant/Funding (institution): Bayer Healthcare Ag; Research grant/Funding (institution): Bbb Technologies Bv; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Boston Pharmaceuticals; Research grant/Funding (institution): Celgene Corporation; Research grant/Funding (institution): Celgene Corporation; Research grant/Funding (institution): Celgene Corporation; Research grant/Funding (institution): Cullinan-Apollo; Research grant/Funding (institution): Debiopharm; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Hoffmann La Roche Ag; Research grant/Funding (institution): Innate Pharma; Research grant/Funding (institution): Institut de Recherche Pierre Fabre; Research grant/Funding (institution): Iris Servier; Research grant/Funding (institution): Janssen Research Foundation; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Lytix Biopharma As; Research grant/Funding (institution): Menarini Ricerche; Research grant/Funding (institution): Merrimack Pharmaceuticals; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Millennium Pharmaceuticals; Research grant/Funding (institution): Molecular Partners Ag; Research grant/Funding (institution): Nektar Therapeutics; Research grant/Funding (institution): Oncoethix; Research grant/Funding (institution): Oncopeptides; Research grant/Funding (institution): Orion Pharma; Research grant/Funding (institution): Ose Pharma; Research grant/Funding (institution): Pierre Fabre; Research grant/Funding (institution): Medicament; Research grant/Funding (institution): Sotio A.S.; Research grant/Funding (institution): Syros Pharmaceuticals; Research grant/Funding (institution): Taiho Pharma; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Xencor. A. Mehta: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Aileron; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Meyers Squibb; Research grant/Funding (institution): Epizyme; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Merck; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Gilead; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Kite; Advisory/Consultancy: Spectrum; Research grant/Funding (institution): ADCT; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Juno Therapeutics; Research grant/Funding (institution): Oncotartis; Research grant/Funding (institution): MiRagen; Speaker Bureau/Expert testimony: Pharmacyclics; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Kite/Gilead. F. Foss: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Acrotech; Honoraria (self), Advisory/Consultancy: Miragen; Honoraria (self), Advisory/Consultancy: Eisai. P. Garfin: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, patient application under review: Seattle Genetics. S. Ansell: Research grant/Funding (institution): Affirmed; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): AI Therapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Trillium; Research grant/Funding (institution): ADC Therapeutics; Full/Part-time employment: Mayo Clinic Rochester.