Zynlonta (loncastuximab tesirine-lpyl)

P2, N=20, Recruiting, University of Washington | N=40 --> 20 | Trial completion date: Jul 2027 --> Jul 2028 | Trial primary completion date: Dec 2026 --> Dec 2027

P2, N=36, Recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Mar 2027

P1/2, N=23, Not yet recruiting, University of Utah

P2, N=49, Recruiting, Fondazione Italiana Linfomi - ETS | Active, not recruiting --> Recruiting

P2, N=50, Recruiting, Istituto Clinico Humanitas | Active, not recruiting --> Recruiting

P2, N=49, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Recruiting --> Active, not recruiting

P3, N=440, Active, not recruiting, ADC Therapeutics S.A. | N=228 --> 440

P2, N=50, Active, not recruiting, Istituto Clinico Humanitas | Recruiting --> Active, not recruiting

Conventional platinum-based or gemcitabine- and bendamustine-containing regimens retain a role for short-term disease control but offer limited durability. In contrast, novel antibody-based therapies, including polatuzumab-containing combinations, loncastuximab tesirine, and tafasitamab plus lenalidomide, have expanded treatment options with improved tolerability. Most notably, CD20 × CD3 bispecific antibodies represent a major therapeutic advance, providing off-the-shelf immune engagement with predominantly outpatient administration. From a practical perspective, early identification of reversible barriers to CAR T-cell therapy and timely use of bispecific antibodies or other antibody-based regimens are critical to achieve rapid disease control, preserve organ function, and, when feasible, restore eligibility for cellular therapy.

P1/2, N=104, Recruiting, Universitaet Muenster

P1/2, N=46, Active, not recruiting, Tanabe Pharma Corporation | Trial primary completion date: Dec 2025 --> Aug 2028

Recently, ADCs have expanded the DLBCL therapeutic landscape, with the approvals of CD79b-targeted polatuzumab vedotin and CD19-directed loncastuximab tesirine for R/R and even frontline disease. However, the clinical application of ADCs is accompanied by challenges, including the management of characteristic toxicities, understanding and overcoming mechanisms of resistance. This review systematically synthesizes the mechanisms of action, updated clinical evidence, toxicity profiles, and resistance mechanisms of ADCs in DLBCL, while also discusses management strategies and provides perspectives on future directions.