Zynlonta
Zynlonta Uses, Dosage, Side Effects, Food Interaction and all others data.
Relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL) are a therapeutic challenge for patients who have undergone prior systemic therapies with limited success. Prognosis is poor and more effective therapies are needed to treat relapsed/refractory cases and improve survival. On April 23 2021, the Food and Drug Administration granted accelerated approval for the antibody-drug conjugate, loncastuximab tesirine-lpyl, also known as Zynlonta. This therapy was developed by ADC Therapeutics and its accelerated approval for relapsed or refractory B-cell lymphoma is based on promising results from the LOTIS-2 clinical trial.
Zynlonta exhibits antitumour activity against malignant B-cells, treating lymphomas. Higher exposure in Cycle 1 of therapy in clinical trials was associated with an increased incidence of Grade ≥2 adverse reactions, including liver function test abnormalities, skin and nail reactions, and liver function testabnormalities.
| Trade Name | Zynlonta |
| Generic | Loncastuximab tesirine |
| Loncastuximab tesirine Other Names | Loncastuximab tesirine, loncastuximab tesirine-lpyl |
| Type | Lyophilized Powder For Injection, For Intravenous Use, Injection, Powder, Lyophilized, For Solution |
| Weight | 151000.0 Da |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zynlonta is an antibody-drug conjugate used for the treatment of relapsed and refractory B-cell lymphomas.
Zynlonta is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma who have undergone two or more prior lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. The above indication is approved under accelerated FDA approval following the results of clinical studies. Continued approval is dependant upon the results of confirmatory clinical trials.
Zynlonta is also used to associated treatment for these conditions: Refractory Large B-cell Lymphoma, Relapsed Large B-cell Lymphoma
How Zynlonta works
Human CD19 antigen is a membrane glycoprotein in the immunoglobulin superfamily expressed in the various stages of B-cell development; it is detected in most malignancies of B-cell origin. Additionally, CD19 has rapid internalization kinetics and does not shed into the general circulation, rendering it a useful therapeutic target for antibody-drug conjugates (ADCs) in the treatment of B-cell malignancies.
Zynlonta is an antibody-drug conjugate designed to target human CD19. It is a humanized monoclonal antibody and conjugated to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin by a protease enzyme cleavable valine-alanine linker. The monoclonal IgG1 kappa antibody component binds to CD19, a transmembrane protein located on B-cell surfaces. The small molecule component, SG3199, functions as a PBD dimer and alkylating agent. Following binding to CD19, loncastuximab tesirine becomes internalized into the cell and subsequently proteolytic cleavage releases the SG3199 component. SG3199 binds to the DNA minor groove, forming cytotoxic DNA interstrand crosslinks, leading to B-cell cell death.
Toxicity
LD50 information for loncastuximab tesirine is not readily available in the literature. Toxicity is increased at higher doses, and may lead to discontinuation.
Food Interaction
No interactions found.Volume of Distribution
In clinical studies, the average loncastuximab tesirine-lpyl volume of distribution was 7.11 liters, with a range between 7.19-8.43 liters.
Elimination Route
Due to its intravenous route of administration, loncastuximab tesirine is readily absorbed into the circulation. Cmax during Cycle 1 of therapy was 2995 μg/L and 3155 μg/L in Cycle 2. AUC was 15,245 - 22,823 μg*day/L during pharmacokinetic studies.
Half Life
The half-life of loncastuximab tesirine-lpyl was 7.06-12.5 days at steady-state.
Clearance
In pharmacokinetic studies, the mean clearance of loncastuximab tesirine-lpyl decreased with time from 0.499 L/day after a single dose to 0.275 L/day at steady-state. One pharmacokinetic study measured a clearance ranging from 0.5-0.64 L/day.
Elimination Route
The main excretion pathways of SG3199 have not been formally studied in humans. SG3199 is thought to be minimally excreted by the kidneys.
Innovators Monograph
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