First‐in‐Human (FIH) Study of the Fully‐Human Kappa‐Lambda CD19/CD47 Bispecific Antibody TG‐1801 in Patients with B‐Cell Lymphoma

Introduction: CD19 is an established target of multiple B-cell lymphoma therapies. Blockade CD47, a macrophage immune checkpoint inhibitory ligand, induces tumor-cell phagocytosis. TG-1801 CD19/CD47 bispecific antibody designed to selectively block CD47 on CD19+ cells, while retaining functional IgG1 Fc domain. Herein we report updated results from the FIH study. Methods: The primary objectives this phase I 3+3 study were characterize safety profile and determine recommended 2 dose (RP2D) as monotherapy in combination with ublituximab. Pharmacokinetics, pharmacodynamics, preliminary antitumor activity also assessed. Eligible patients (pts) had relapsed/refractory (R/R) after ≥1 prior standard therapy. doses evaluated included: 20 mg, 60 180 360 & 500 mg. In arm, treatment consisted weekly fixed dosing 1h-infusions 4-week cycle: day (D)1, D8, D15, D22 cycle (C) 1 C2. Pts who at least stable disease cycles continued once every 4 weeks for further infusions. Intra-pt escalations permitted. A second arm explored ublituximab; anti-CD20 mAb. received ublituximab, IV weeks: D1, D15 C1; D1 C2-C6; C9 3 thereafter, up 24 cycles. levels (300 mg 400 mg) 900 ublituximab tested. Responses assessed by Lugano 2014 criteria. Results: As October 2022, 14 pts (MZL = 5, DLBCL including Richter’s transformation FL 4) 16 therapy (DLBCL 9, 4, MZL 2, MCL 1). median therapies (range, 1–8) (53%) refractory their last One DLT grade (G) thrombocytopenia occurred monotherapy. Most frequent (>20%) emergent adverse events (TEAEs) (n 10) included fatigue, thrombocytopenia, infusion-related reaction (3 each), no G3/4 TEAEs occurring >20% pts. Combination was well tolerated (TG-1801 300 N 3, 13) without DLT. common (≥20%) anemia, headache, fatigue (5 permanently discontinued due (1 infusion [500 monotherapy], rash [360 monotherapy]). Among 13 evaluable pts, there (ORR 23%) partial responses (PR). 16), 44% ORR observed complete response (CR) pt 6 PR FL) 56% 50% FL. research funded by: TG Therapeutics Inc. Keywords: Therapies, Immunotherapy, Targeting Tumor Microenvironment Conflicts interests pertinent abstract. E. A. Hawkes Consultant or advisory role: Advisory board speaker fees (institutional personal) Roche, Merck Sharpe Dohme, Astra Zeneca, Gilead, Antigene, Novartis, Regeneron, Janssen, Specialised Therapeutics, outside submitted work Research funding: Bristol Myers Squibb, KgA, Zeneca K. L. Lewis Astrazeneca, Loxo/Lilly, IQVIA, MSD Honoraria: Roche H. P. Miskin Employment leadership position: Stock ownership: Sportelli S. Kolibaba Normant T. Turpuseema C. Y. Cheah AstraZenecca, Lilly, therapeutics, Beigene, Menarini, Daizai, Abbvie, Genmab. BMS BMS, Abbvie; MSD, Lilly