Zynlonta (loncastuximab tesirine-lpyl)

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.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2030 | Trial primary completion date: Jan 2026 --> Jan 2030

P2, N=26, Recruiting, University of Miami | Not yet recruiting --> Recruiting

P3, N=440, Active, not recruiting, ADC Therapeutics S.A. | Trial primary completion date: Jun 2025 --> Jan 2026

There are several FDA-approved anti-CD19 CAR-T cells, including Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel, as well as anti-CD19 monoclonal antibodies (mABs), such as loncastuximab tesirine and tafasitamab...Blinatumomab, the inaugural FDA-approved antibody to be produced using BiTE technology, has demonstrated notable benefits in clinical trials investigating its use in the treatment of B-cell acute lymphoblastic leukemia (B-ALL)...Furthermore, we engaged in a discourse on the various treatment options concerning CD19 targeting, accompanied by an exposition of the pertinent clinical studies. In this regard, the efficacy, safety, and limitations of each option were thoroughly delineated.

P1, N=11, Active, not recruiting, Medical College of Wisconsin | N=33 --> 11 | Trial completion date: May 2026 --> Oct 2027 | Trial primary completion date: May 2026 --> May 2025 | Recruiting --> Active, not recruiting