Loncastuximab tesirine

Loncastuximab tesirine
Monoclonal antibody
Type	Whole antibody
Source	Humanized
Target	CD19
Clinical data
Pronunciation	LON-kas-TUK-sih-mab TEH-sih-reen
Trade names	Zynlonta
Other names	ADCT-402, loncastuximab tesirine-lpyl
License data	US DailyMed: Loncastuximab_tesirine;
Routes of; administration	Intravenous
ATC code	None;
Legal status
Legal status	US: ℞-only ;
Identifiers
CAS Number	1879918-31-6;
DrugBank	DB16222;
ChemSpider	none;
UNII	7K5O7P6QIU;
KEGG	D11338;
Chemical and physical data
Formula	C6544H10048N1718O2064S52
Molar mass	147481.45 g·mol−1

Loncastuximab tesirine , sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma.^[1] It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.^[1]

Loncastuximab tesirine was approved for medical use in the United States in April 2021.^[1]^[2]

Medical uses[]

Loncastuximab tesirine is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma.^[1]

Technology[]

The humanized monoclonal antibody is stochastically conjugated via a valine-alanine cleavable, maleimide linker to a cytotoxic (anticancer) pyrrolobenzodiazepine (PBD) dimer.^{[medical citation needed]} The antibody binds to CD19, a protein which is highly expressed on the surface of B-cell hematological tumors^[3] including certain forms of lymphomas and leukemias.^{[medical citation needed]} After binding to the tumor cells the antibody is internalized, the cytotoxic drug PBD is released and the cancer cells are killed.^{[medical citation needed]} PBD dimers are generated out of PBD monomers, a class of natural products produced by various actinomycetes. PBD dimers work by crosslinking specific sites of the DNA, blocking the cancer cells’ division that cause the cells to die.^{[medical citation needed]} As a class of DNA-crosslinking agents they are significantly more potent than systemic chemotherapeutic drugs.^[4]

Clinical trials[]

Two phase I trials are evaluating the medication in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma and relapsed or refractory B-cell acute lymphoblastic leukemia.^[5] At the 14th International Conference on Malignant Lymphoma interim results from a Phase I, open-label, dose-escalating study designed to evaluate the treatment of loncastuximab tesirine in relapsed or refractory non-Hodgkin’s lymphoma were presented.^[6] Among the patients enrolled at the time of the data cutoff the overall response rate was 61% in the total patient population (42% complete response and 19% partial response) and in patients with relapsing or refractory diffuse large B-cell lymphoma (DLBCL) the overall response rate was 57% (43% complete response and 14% partial response).^[7]^[8]

Orphan drug designation[]

Loncastuximab tesirine was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma.^[9]

References[]

^ Jump up to: ^a ^b ^c ^d ^e "Zynlonta- loncastuximab tesirine injection, powder, lyophilized, for solution". DailyMed. Retrieved 1 June 2021.
^ "Drug Approval Package: Zynlonta". U.S. Food and Drug Administration (FDA). 24 May 2021. Retrieved 1 June 2021.
^ Wang K, Wei G, Liu D (November 2012). "CD19: a biomarker for B cell development, lymphoma diagnosis and therapy". Experimental Hematology & Oncology. 1 (1): 36. doi:10.1186/2162-3619-1-36. PMC 3520838. PMID 23210908.
^ "Pyrrolobenzodiazepine". ADC Review.
^ Clinical trial number NCT02669017 for "ADCT-402 in B-NHL" at ClinicalTrials.gov
^ Kahl B, Hamadani M, Caimi PF, Reid EG, Havenith K, He S, Feingold JM, O'Connor O (June 2017). "First clinical results of ADCT‐402, a novel pyrrolobenzodiazepine-based antibody drug conjugate (ADC), in relapsed/refractory B‐cell linage NHL" (PDF). Hematol Oncol. 35 (S2): 49–51. doi:10.1002/hon.2437_33.
^ "First clinical results of ADCT-402". ADC Review. 16 June 2017.
^ Bainbridge K (3 July 2017). "Grandfather fighting deadly cancer reveals scans of tumors after testing new drug". Mirror.
^ "Loncastuximab tesirine Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 8 June 2017. Retrieved 1 June 2021.

External links[]

"Loncastuximab tesirine". Drug Information Portal. U.S. National Library of Medicine.
"Loncastuximab tesirine-lpyl". NCI Drug Dictionary. National Cancer Institute.
"Loncastuximab tesirine-lpyl". National Cancer Institute. 21 May 2021.
Clinical trial number NCT03589469 for "Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (LOTIS-2)" at ClinicalTrials.gov

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[Zynlonta_FDA_label-1] Jump up to: ^a ^b ^c ^d ^e "Zynlonta- loncastuximab tesirine injection, powder, lyophilized, for solution". DailyMed. Retrieved 1 June 2021.

[2] "Drug Approval Package: Zynlonta". U.S. Food and Drug Administration (FDA). 24 May 2021. Retrieved 1 June 2021.

[pmid23210908-3] Wang K, Wei G, Liu D (November 2012). "CD19: a biomarker for B cell development, lymphoma diagnosis and therapy". Experimental Hematology & Oncology. 1 (1): 36. doi:10.1186/2162-3619-1-36. PMC 3520838. PMID 23210908.

[4] "Pyrrolobenzodiazepine". ADC Review.

[5] Clinical trial number NCT02669017 for "ADCT-402 in B-NHL" at ClinicalTrials.gov

[6] Kahl B, Hamadani M, Caimi PF, Reid EG, Havenith K, He S, Feingold JM, O'Connor O (June 2017). "First clinical results of ADCT‐402, a novel pyrrolobenzodiazepine-based antibody drug conjugate (ADC), in relapsed/refractory B‐cell linage NHL" (PDF). Hematol Oncol. 35 (S2): 49–51. doi:10.1002/hon.2437_33.

[7] "First clinical results of ADCT-402". ADC Review. 16 June 2017.

[8] Bainbridge K (3 July 2017). "Grandfather fighting deadly cancer reveals scans of tumors after testing new drug". Mirror.

[9] "Loncastuximab tesirine Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 8 June 2017. Retrieved 1 June 2021.

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