June 30, 2022

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2021 New Antibody drug: Loncastuximab tesirine-lpyl (Zynlonta)

2021 New Antibody drug: Loncastuximab tesirine-lpyl (Zynlonta)

 


2021 New Antibody drug: Loncastuximab tesirine-lpyl (Zynlonta). On April 23, 2021, the U.S. Food and Drug Administration (FDA) first approved loncastuximab tesirine-lpyl (trade name Zynlonta) for the treatment of relapsed or refractory (r /r) Adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), DLBCL originating from low-grade lymphoma and high-grade cell lymphoma.

Zynlonta is an antibody-conjugated drug (ADC) that targets CD19. It consists of a humanized anti-human CD19 monoclonal antibody and pyrrolobenzodiazepine (PBD) dimer cytotoxin through a connector. Coupled.

It is worth mentioning that Zynlonta is the first and only CD19-targeted ADC. Previously, Zynlonta received accelerated approval through the priority review process. This accelerated approval is based on positive data from the key LOTIS-2 clinical trial.

2021 New Antibody drug: Loncastuximab tesirine-lpyl (Zynlonta)

The recommended dose of Zynlonta is: 0.15 mg/kg intravenous infusion every 3 weeks for 2 consecutive cycles; thereafter 0.075 mg/kg per cycle every 3 weeks. Zynlonta was developed by the Swiss pharmaceutical company ADC Therapeutics SA. In China, Zynlonta is being developed by Overland ADCT BioPharma, a joint venture established by ADC Therapeutics and Overland Pharmaceuticals.

 

Pharmacodynamics and pharmacokinetics

The active pharmaceutical ingredient of Zynlonta is loncastuximab tesirine, which is an antibody-conjugated drug targeting CD19. A humanized anti-human CD19 monoclonal antibody dimerizes with pyrrolobenzodiazepine (PBD) through a connector. Somatic cell toxin conjugated.

Once bound to CD19-expressing cells, loncastuximab tesirine will be internalized by the cell, and then release cytotoxin, the toxin can irreversibly bind to DNA, resulting in strong inter-strand cross-links that prevent DNA strand separation, thereby disrupting replication. The process of DNA metabolism eventually leads to cell death. CD19 is a proven popular target for the treatment of B-cell malignancies.

2021 New Antibody drug: Loncastuximab tesirine-lpyl (Zynlonta)

The above table shows the steady-state plasma exposure in the second cycle at the recommended dose approved by Zynlonta. The steady-state Cmax of Zynlonta is 28.2% lower than the Cmax after the first administration, and the time to steady-state is 210 days.

The average volume of distribution (CV%) of Zynlonta is 7.11 L (26.6%). The average clearance rate of Zynlonta decreased over time, from 0.499 liters/day (89.3%) after a single dose to 0.275 liters/day (38.2%) at steady state. In steady state, the average half-life of Zynlonta is 20.8 days.

 

Clinical Trials

The efficacy of Zynlonta was evaluated in the LOTIS-2 clinical trial (NCT03589469), an open-label one-arm trial that enrolled 145 adult patients with relapsed or refractory diffuse large B-cell lymphoma. These The patient underwent at least 2 systemic treatments.

The patient took Zynlonta 0.15 mg/kg every 3 weeks for 2 consecutive cycles, and then took Zynlonta 0.075 mg/kg every 3 weeks in subsequent cycles until the disease progressed or unacceptable toxicity appeared.

Among the 145 patients enrolled, the median age was 66 years (23-94 years), 59% were male, and 94% of the patients had an ECOG performance of 0-1. Of these patients, 90% are white, 3% are black, and 2% are Asian.

The median of previous treatments was 3 (range 2-7), 63% were refractory diseases, 17% were previous stem cell transplantation, and 9% were previous chimeric antigen receptor (CAR) T cell therapy.


The efficacy endpoint is based on the overall response rate (ORR) assessed by the Independent Review Committee (IRC) using the Lugano 2014 standard. The median follow-up time was 7.3 months (range 0.3 to 20.2), and the median time from initiation of treatment to remission was 1.3 months (range 1.1 to 8.1).

2021 New Antibody drug: Loncastuximab tesirine-lpyl (Zynlonta)

The results showed that the ORR of Zynlonta monotherapy was 48.3% (70/145 cases), the complete response rate (CR) was 24.1% (35/145 cases), and the partial response rate (PR) was 24.1 (35/145 cases). Among 70 patients in remission, the median duration of remission (DOR) was 10.3

 

(source:internet, reference only)


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