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DRUG CLASS:

CD19-targeted antibody-drug conjugate

3d
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
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TNFRSF8 (TNF Receptor Superfamily Member 8) • CD79B (CD79b Molecule) • CD22 (CD22 Molecule)
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Rituxan (rituximab) • Zynlonta (loncastuximab tesirine-lpyl) • Polivy (polatuzumab vedotin-piiq)
25d
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
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Zynlonta (loncastuximab tesirine-lpyl)
2ms
Enrollment open
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Epkinly (epcoritamab-bysp) • Zynlonta (loncastuximab tesirine-lpyl)
3ms
Trial primary completion date
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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gemcitabine • Rituxan (rituximab) • oxaliplatin • Zynlonta (loncastuximab tesirine-lpyl)
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
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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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
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CD20 (Membrane Spanning 4-Domains A1)
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CD20 positive
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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
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CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
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clonoSEQ
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Calquence (acalabrutinib) • Zynlonta (loncastuximab tesirine-lpyl)
4ms
IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas (clinicaltrials.gov)
P1, N=140, Recruiting, Iksuda Therapeutics Ltd. | Trial completion date: Sep 2027 --> Sep 2028 | Trial primary completion date: Sep 2025 --> Sep 2026
Trial completion date • Trial primary completion date
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CD19 positive
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IKS03
5ms
Trial completion date • Trial primary completion date
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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
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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Zynlonta (loncastuximab tesirine-lpyl)
7ms
Enrollment open • IO biomarker
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Rituxan (rituximab) • Zynlonta (loncastuximab tesirine-lpyl)