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    DRUG:

    Zynlonta (loncastuximab tesirine-lpyl)

    i
    Other names: ADCT-402, ADCT 402, anti-CD19 PBD-conjugate, MT-2111, ADCT402, MT2111, MT 2111
    Company:
    Mitsubishi Tanabe, Overland ADCT BioPharma, SOBI
    Drug class:
    DNA replication inhibitor, CD19-targeted antibody-drug conjugate
    Related drugs:
    2d
    Beyond R-CHOP: The rise of antibody-drug conjugates in DLBCL. (PubMed, Blood Rev)
    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.
    Review • Journal
    |
    TNFRSF8 (TNF Receptor Superfamily Member 8) • CD79B (CD79b Molecule) • CD22 (CD22 Molecule)
    |
    Rituxan (rituximab) • Zynlonta (loncastuximab tesirine-lpyl) • Polivy (polatuzumab vedotin-piiq)
    24d
    A Phase II Study of Loncastuximab Tesirine as Consolidation Strategy in Patients With LBCL in PR After CAR T-cell Therapy (clinicaltrials.gov)
    P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2030 | Trial primary completion date: Jan 2026 --> Jan 2030
    Trial completion date • Trial primary completion date
    |
    Zynlonta (loncastuximab tesirine-lpyl)
    2ms
    EPCOR+LONCA: Epcoritamab in Combination With Loncastuximab Tesirine in Relapsed/Refractory Large B-cell Lymphoma (clinicaltrials.gov)
    P2, N=26, Recruiting, University of Miami | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Epkinly (epcoritamab-bysp) • Zynlonta (loncastuximab tesirine-lpyl)
    3ms
    LOTIS 5: Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov)
    P3, N=440, Active, not recruiting, ADC Therapeutics S.A. | Trial primary completion date: Jun 2025 --> Jan 2026
    Trial primary completion date
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    gemcitabine • Rituxan (rituximab) • oxaliplatin • Zynlonta (loncastuximab tesirine-lpyl)
    3ms
    Exploring CD19-targeted Immunotherapy Strategies for Human B-cell Lymphoma. (PubMed, Arch Razi Inst)
    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.
    Review • Journal
    |
    CD20 (Membrane Spanning 4-Domains A1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • CD79B (CD79b Molecule) • CD52 (CD52 Molecule)
    |
    Blincyto (blinatumomab) • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • Zynlonta (loncastuximab tesirine-lpyl) • Monjuvi (tafasitamab-cxix)
    4ms
    Loncastuximab Tesirine in Combination With DA-EPOCH-R in Patients With Previously Untreated Aggressive B-cell Lymphoid Malignancies (clinicaltrials.gov)
    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
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    Rituxan (rituximab) • cyclophosphamide • etoposide IV • pegylated liposomal doxorubicin • vincristine • prednisone • Zynlonta (loncastuximab tesirine-lpyl) • Marqibo (vincristine liposomal)
    4ms
    Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov)
    P2, N=36, Recruiting, City of Hope Medical Center | Trial completion date: Aug 2025 --> Apr 2026 | Trial primary completion date: Aug 2025 --> Apr 2026
    Trial completion date • Trial primary completion date
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 positive
    |
    Zynlonta (loncastuximab tesirine-lpyl) • Lunsumio (mosunetuzumab-axgb)
    4ms
    Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1, N=24, Active, not recruiting, University of Alabama at Birmingham | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
    |
    clonoSEQ
    |
    Calquence (acalabrutinib) • Zynlonta (loncastuximab tesirine-lpyl)
    5ms
    LOTIS 7: A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7) (clinicaltrials.gov)
    P1, N=200, Recruiting, ADC Therapeutics S.A. | Trial completion date: Dec 2026 --> Oct 2027 | Trial primary completion date: Dec 2025 --> Oct 2026
    Trial completion date • Trial primary completion date
    |
    Gazyva (obinutuzumab) • Zynlonta (loncastuximab tesirine-lpyl) • Polivy (polatuzumab vedotin-piiq) • Lunsumio (mosunetuzumab-axgb) • Columvi (glofitamab-gxbm)
    7ms
    A Study of MT-2111 in Patients With Relapsed/Refractory DLBCL (clinicaltrials.gov)
    P1/2, N=46, Active, not recruiting, Mitsubishi Tanabe Pharma Corporation | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    Zynlonta (loncastuximab tesirine-lpyl)
    7ms
    Loncastuximab Tesirine and Rituximab as Bridging Therapy Prior to Standard-of-care CD19 CAR T-cell Therapy in Patients With Large B-cell Lymphoma (clinicaltrials.gov)
    P2, N=29, Recruiting, University of Utah | Not yet recruiting --> Recruiting
    Enrollment open • IO biomarker
    |
    Rituxan (rituximab) • Zynlonta (loncastuximab tesirine-lpyl)