Abstract 558TiP
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.
Editorial acknowledgement
Medical writing support was provided by Suparna Abraham, PharmD, and editorial support by Travis Taylor, BA, all of Scion, London, supported by Seagen Inc.
Legal entity responsible for the study
Seagen.
Funding
Has not received any funding.
Disclosure
V. Ribrag: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: immune design; Financial Interests, Personal, Advisory Board: incyte; Financial Interests, Personal, Advisory Board: infinity pharma; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Nanostring; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Roche/genetech; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: AZD; Financial Interests, Institutional, Research Grant: Argen-X; Financial Interests, Institutional, Research Grant: Epizyme; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Astex Pharma. D. Davar: Financial Interests, Advisory Board: Instil Bio; Financial Interests, Advisory Board: Shionogi; Financial Interests, Advisory Board: Vedanta Biosciences; Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Advisory Board: Immunocore; Financial Interests, Advisory Board: Merk; Financial Interests, Advisory Board: Tesaro; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Checkmate Pharma; Financial Interests, Institutional, Research Grant: CellSight Tech; Financial Interests, Institutional, Research Grant: MedPacto; Financial Interests, Institutional, Research Grant: Merk; Financial Interests, Institutional, Research Grant: Zucero Therapeutics. E. Garralda: Financial Interests, Advisory Board: Alkermes; Financial Interests, Advisory Board: Anaveon; Financial Interests, Advisory Board: Boehringer Ingelheim; Financial Interests, Advisory Board: BMS; Financial Interests, Advisory Board: Ellipses Pharma; Financial Interests, Advisory Board: Janssen; Financial Interests, Advisory Board: MabDiscovery; Financial Interests, Advisory Board: NeoMed; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Seagen; Financial Interests, Advisory Board: Thermo Fischer Scientific; Financial Interests, Institutional, Research Grant: AZD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Taiho Oncology; Financial Interests, Institutional, Research Grant: Thermo Fisher Scientific; Financial Interests, Invited Speaker: Lilly; Financial Interests, Invited Speaker: MSD; Financial Interests, Invited Speaker: Roche; Financial Interests, Invited Speaker: Thermo Fischer Scientific. G. Curigliano: Financial Interests, Advisory Board: AZD; Financial Interests, Advisory Board: Boehringer Ingelheim; Financial Interests, Advisory Board: BMS; Financial Interests, Advisory Board: Daiicho Sankyo; Financial Interests, Advisory Board: Foundation Medicine; Financial Interests, Advisory Board: GSK; Financial Interests, Advisory Board: Lilly; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Roche/genentech; Financial Interests, Advisory Board: Samsung; Financial Interests, Advisory Board: Seagen; Financial Interests, Advisory Board: Ellispses Pharma; Financial Interests, Invited Speaker: Daiichi Sankyo; Financial Interests, Invited Speaker: Foundation Medicine; Financial Interests, Invited Speaker: Lilly; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker: Pfizer; Financial Interests, Invited Speaker: Roche/Genentech; Financial Interests, Invited Speaker: Samsung; Financial Interests, Invited Speaker: Seagen. J. Zain: Financial Interests, Advisory Board: Legend Biotech; Financial Interests, Advisory Board: Ono Pharma; Financial Interests, Advisory Board: Secura Bio; Financial Interests, Advisory Board: Verastem; Financial Interests, Advisory Board: Kiyowa Kirin; Financial Interests, Advisory Board: Mundipharma; Financial Interests, Advisory Board: Seagen; Financial Interests, Institutional, Research Grant: Affimed Therapeutics; Financial Interests, Institutional, Research Grant: CRSPR; Financial Interests, Institutional, Research Grant: Onco Taris; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Secura Bio; Financial Interests, Invited Speaker: Celgene; Financial Interests, Invited Speaker: Mallinckrodt; Financial Interests, Invited Speaker: Seagen. A. Mehta: Financial Interests, Advisory Board: Aileron Therapeutics; Financial Interests, Advisory Board: AZD; Financial Interests, Advisory Board: BMS; Financial Interests, Advisory Board: Carevive; Financial Interests, Advisory Board: Incyte; Financial Interests, Advisory Board: Kite Pharma; Financial Interests, Advisory Board: Kyowa Kirin; Financial Interests, Advisory Board: Pharmacyclics; Financial Interests, Advisory Board: Rigel; Financial Interests, Advisory Board: Seagen; Financial Interests, Advisory Board: Spectrum Pharma; Financial Interests, Advisory Board: TG Therapeutics; Financial Interests, Institutional, Research Grant: ADC Therapeutics; Financial Interests, Institutional, Research Grant: Affirmed; Financial Interests, Institutional, Research Grant: Aileron; Financial Interests, Institutional, Research Grant: Astexa Pharma; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Carevive; Financial Interests, Institutional, Research Grant: Epizyme; Financial Interests, Institutional, Research Grant: Forty Seven; Financial Interests, Institutional, Research Grant: Gilead; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Innate Pharma; Financial Interests, Institutional, Research Grant: Juno; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Oncotartis; Financial Interests, Institutional, Research Grant: Pharmacyclics/Janssen; Financial Interests, Institutional, Research Grant: Rhizen Pharma; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: TG Therapeutics; Financial Interests, Invited Speaker: AZ; Financial Interests, Invited Speaker: Gilead; Financial Interests, Invited Speaker: Incyte; Financial Interests, Invited Speaker: ite Pharma; Financial Interests, Invited Speaker: Seagen; Financial Interests, Invited Speaker: Spectrum Pharma. A. Minchom: Financial Interests, Advisory Board: Janssen; Financial Interests, Advisory Board: Bayer; Financial Interests, Advisory Board: Chugai Pharma; Financial Interests, Advisory Board: Faron Pharma; Financial Interests, Advisory Board: Merck; Financial Interests, Advisory Board: Novartis; Financial Interests, Institutional, Research Grant: Seagen. R.E. Sanborn: Financial Interests, Advisory Board: AZD; Financial Interests, Advisory Board: Blueprint Medicines; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: EMD Serono; Financial Interests, Advisory Board: Roche/Genentech; Financial Interests, Advisory Board: Janssen; Financial Interests, Advisory Board: Lilly; Financial Interests, Advisory Board: Macrogenics; Financial Interests, Advisory Board: Amgen; Financial Interests, Institutional, Research Grant: AZD; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Medimmune; Financial Interests, Institutional, Research Grant: Merk. F. Foss: Financial Interests, Advisory Board: Acrotech Biopharma; Financial Interests, Advisory Board: Esai; Financial Interests, Advisory Board: Mallinckrodt; Financial Interests, Advisory Board: miRagen; Financial Interests, Advisory Board: Portola; Financial Interests, Advisory Board: Seagen; Financial Interests, Advisory Board: Verastem; Financial Interests, Institutional, Research Grant: Astex Pharma; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Esai; Financial Interests, Institutional, Research Grant: Kura Oncology; Financial Interests, Institutional, Research Grant: Kyowa Kirin; Financial Interests, Institutional, Research Grant: Miragen; Financial Interests, Invited Speaker: Seagen. A. Forero-Torres: Financial Interests, Member: Seagen; Financial Interests, Ownership Interest: Seagen. S. Ansell: Financial Interests, Advisory Board: Research to Practice; Financial Interests, Advisory Board: WebMD; Financial Interests, Institutional, Research Grant: A1 Therapeutics; Financial Interests, Institutional, Research Grant: ADC Therapeutics; Financial Interests, Institutional, Research Grant: Affirmed Therapeutics; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Trillium Therapeutics. All other authors have declared no conflicts of interest.