Loncastuximab Tesirine
drugOn this page
Also known as ADCT-402Adct-402 tesirineLoncastuximab tesirinaLoncastuximab tesirine lpylLoncastuximab tesirine-lpylZynlonta
Summary
Loncastuximab Tesirine (CHEMBL4297778) is an approved antibody drug conjugate (ATC L01FX22) targeting CD19; indicated across 12 conditions including diffuse large b-cell lymphoma and b-cell non-hodgkin lymphoma.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Antibody drug conjugate
- ATC class: L01FX22
- Targets: 1 (CD19)
- Indications: 12 conditions
- Clinical trials: 31
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4297778 |
| Name | Loncastuximab Tesirine |
| Type | Antibody drug conjugate |
| Max phase | 4 |
| ATC | L01FX22 |
Also known as: ADCT-402, Adct-402 tesirine, ADCT-402 TESIRINE, Loncastuximab tesirina, Loncastuximab tesirine, Loncastuximab tesirine lpyl, Loncastuximab tesirine-lpyl, Zynlonta, LONCASTUXIMAB TESIRINE
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| CD19 | CD19 | Binding | 2.5% | P15391 |
Bioactivity
No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).
Target pathways
Aggregated over 1 target gene(s): CD19.
Top Reactome pathways
17 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| PIP3 activates AKT signaling | 1 | CD19 |
| Adaptive Immune System | 1 | CD19 |
| Signal Transduction | 1 | CD19 |
| Disease | 1 | CD19 |
| Complement cascade | 1 | CD19 |
| Innate Immune System | 1 | CD19 |
| Immune System | 1 | CD19 |
| Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 1 | CD19 |
| Negative regulation of the PI3K/AKT network | 1 | CD19 |
| PI3K/AKT Signaling in Cancer | 1 | CD19 |
| Constitutive Signaling by Aberrant PI3K in Cancer | 1 | CD19 |
| Diseases of signal transduction by growth factor receptors and second messengers | 1 | CD19 |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1 | CD19 |
| Intracellular signaling by second messengers | 1 | CD19 |
| Regulation of Complement cascade | 1 | CD19 |
| Antigen activates B Cell Receptor (BCR) leading to generation of second messengers | 1 | CD19 |
| Signaling by the B Cell Receptor (BCR) | 1 | CD19 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| B-1 B cell differentiation | 1 |
| B cell proliferation involved in immune response | 1 |
| immunoglobulin mediated immune response | 1 |
| B cell proliferation | 1 |
| antigen receptor-mediated signaling pathway | 1 |
| B cell receptor signaling pathway | 1 |
| regulation of B cell receptor signaling pathway | 1 |
| regulation of B cell activation | 1 |
| positive regulation of release of sequestered calcium ion into cytosol | 1 |
| positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1 |
| adaptive immune response | 1 |
| immune system process | 1 |
| B cell mediated immunity | 1 |
Indications & clinical
Indications
12 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| diffuse large B-cell lymphoma | 4 | MONDO:0018905 | EFO:0000403 |
| B-cell non-Hodgkin lymphoma | 4 | MONDO:0015759 | EFO:1001938 |
| neoplasm | 4 | MONDO:0005070 | EFO:0000616 |
| B-cell neoplasm | 4 | MONDO:0004095 | MONDO:0004095 |
| follicular lymphoma | 2 | MONDO:0018906 | MONDO:0018906 |
| neoplasm of mature B-cells | 2 | MONDO:0004949 | EFO:0000096 |
| non-Hodgkin lymphoma | 2 | MONDO:0018908 | EFO:0005952 |
| Waldenstrom macroglobulinemia | 2 | MONDO:0100280 | EFO:0009441 |
| mantle cell lymphoma | 2 | MONDO:0018876 | EFO:1001469 |
| acute lymphoblastic leukemia | 1 | MONDO:0004967 | EFO:0000220 |
| Burkitt lymphoma | 1 | MONDO:0007243 | EFO:0000309 |
| B-cell chronic lymphocytic leukemia | 1 | MONDO:0004948 | EFO:0000095 |
Clinical trials
Total trials: 31.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 15 |
| PHASE1 | 11 |
| PHASE1/PHASE2 | 2 |
| PHASE3 | 1 |
| PHASE2/PHASE3 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04384484 | PHASE3 | ACTIVE_NOT_RECRUITING | Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma |
| NCT05991388 | PHASE2/PHASE3 | RECRUITING | A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma |
| NCT04998669 | PHASE2 | RECRUITING | Loncastuximab Tesirine in Combination With Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma |
| NCT05190705 | PHASE2 | ACTIVE_NOT_RECRUITING | Loncastuximab Tesirine in WM |
| NCT05296070 | PHASE2 | RECRUITING | Open-label of Loncastuximab Tesirine (ADCT-402) in Relapsed/Refractory Marginal Zone Lymphoma |
| NCT05453396 | PHASE2 | RECRUITING | Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies |
| NCT05464719 | PHASE2 | RECRUITING | A Phase II Study of Loncastuximab Tesirine as Consolidation Strategy in Patients With LBCL in PR After CAR T-cell Therapy |
| NCT05600686 | PHASE2 | RECRUITING | Loncastuximab Tesirine and Rituximab Followed by DA-EPOCH-R for Treating Patients With High-Risk Diffuse Large B-cell Lymphoma |
| NCT05672251 | PHASE2 | RECRUITING | Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma |
| NCT06788964 | PHASE2 | RECRUITING | Loncastuximab Tesirine and Rituximab as Bridging Therapy Before Standard-of-care CAR-T Therapy in Patients With Large B-cell Lymphoma (CORAL) |
| NCT06918912 | PHASE2 | RECRUITING | Study of Loncastuximab Tesirine in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) Following CAR-T Therapy Failure |
| NCT06919939 | PHASE2 | RECRUITING | Epcoritamab in Combination With Loncastuximab Tesirine in Relapsed/Refractory Large B-cell Lymphoma |
| NCT07197307 | PHASE2 | NOT_YET_RECRUITING | Combining Loncastuximab Tesirine and Epcoritamab in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) |
| NCT07573436 | PHASE1/PHASE2 | NOT_YET_RECRUITING | Loncastuximab Tesirine and Rituximab as First-line Therapy in Patients With Post-transplant Lymphoproliferative Disorder (PLUTO) |
| NCT03589469 | PHASE2 | COMPLETED | Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma |
| NCT03684694 | PHASE1/PHASE2 | TERMINATED | Safety and Efficacy Study of Loncastuximab Tesirine + Ibrutinib in Diffuse Large B-Cell or Mantle Cell Lymphoma |
| NCT04699461 | PHASE2 | TERMINATED | Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma |
| NCT05144009 | PHASE2 | TERMINATED | A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL) |
| NCT05222438 | PHASE2 | WITHDRAWN | Trial of Loncastuximab Tesirine in High Risk Diffuse Large B-cell Lymphoma Post Transplant |
| NCT04970901 | PHASE1 | RECRUITING | 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) |
| NCT05053659 | PHASE1 | ACTIVE_NOT_RECRUITING | Loncastuximab Tesirine and Venetoclax for Relapsed/ Refractory Non-Hodgkin Lymphoma |
| NCT05270057 | PHASE1 | ACTIVE_NOT_RECRUITING | Loncastuximab Tesirine in Combination With DA-EPOCH-R in Patients With Previously Untreated Aggressive B-cell Lymphoid Malignancies |
| NCT05660395 | PHASE1 | RECRUITING | A Study to Evaluate the Pharmacokinetics and Safety of Loncastuximab Tesirine in Participants With Relapsed or Refractory Diffuse Large B-cell Lymphoma or High-grade B-cell Lymphoma With Hepatic Impairment (LOTIS-10) |
| NCT05971251 | PHASE1 | ACTIVE_NOT_RECRUITING | Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia |
| NCT06607549 | PHASE1 | RECRUITING | Loncastuximab Tesirine and Rituximab Following Stereotactic Radiosurgery in Patients With Central Nervous System Lymphomas (SOLAR) |
| NCT02669017 | PHASE1 | COMPLETED | Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL) |
| NCT02669264 | PHASE1 | TERMINATED | Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Acute Lymphoblastic Leukemia (B-ALL) |
| NCT03685344 | PHASE1 | TERMINATED | Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma |
| NCT04974996 | PHASE1 | WITHDRAWN | A Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of Loncastuximab Tesirine in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated Diffuse Large B-cell Lymphoma (LOTIS-8) |
| NCT05228249 | PHASE1 | WITHDRAWN | Loncastuximab Tesirine in Combination With Chemotherapy Prior to Stem Cell Transplant for the Treatment of Recurrent or Refractory Diffuse Large B-Cell Lymphoma |
| NCT04705454 | Not specified | NO_LONGER_AVAILABLE | Loncastixumab Tesirine (ADCT-402) Expanded Access Program (EAP) for Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).
Related Atlas pages
- Genes: CD19
- Diseases: diffuse large B-cell lymphoma, B-cell non-Hodgkin lymphoma, neoplasm, B-cell neoplasm