Zynlonta is an ADC composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Upon binding to CD19, Zynlonta is internalized where enzymes release the cytotoxic PBD-based dimer, which binds to DNA to create interstrand cross-links. These cross-links are designed to disrupt DNA metabolic processes such as replication, which ultimately lead to cell death.

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FDA Approval of ZYNLONTA™ (loncastuximab
tesirine-lpyl) - First CD19-targeted ADC
The US FDA has approved Zynlonta (loncastuximab tesirine), the eleventh antibody-drug
conjugate (ADC) and the first for ADC Therapeutics. It is the first and only
CD19-targeted ADC as a single-agent treatment for adult patients with relapsed or
refractory (r/r) diffuse large B-cell lymphoma (DLBCL).
DLBCL is the most common type of non-Hodgkin lymphoma, a rapidly progressing
aggressive disease. More than 40% of first-line DLBCL therapies fail, and the prognosis is
poor for patients whose first-line therapy fails. Therefore, effective and innovative
treatments are urgently needed.
Antibody-conjugated drugs combine with specific antigens on the surface of cancer cells
to deliver the toxic compounds carried into the cells, thereby killing cancer cells while
avoiding damage to healthy cells. Zynlonta is an ADC composed of a humanized
monoclonal antibody directed against human CD19 and conjugated through a
linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Upon binding to CD19,
Zynlonta is internalized where enzymes release the cytotoxic PBD-based dimer, which
binds to DNA to create interstrand cross-links. These cross-links are designed to disrupt
DNA metabolic processes such as replication, which ultimately lead to cell death.

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Image source: ADC Therapeutics Official Website
The FDA approval is based on a single-arm Phase 2 clinical trial called LOTIS-2, which
enrolled 145 patients with relapsed/refractory DLBCL. These patients have previously
received at least two therapies, and some of them have received stem cell transplantation
therapy and CAR-T therapy. The test results showed that Zynlonta achieved an overall
response rate (ORR) of 48.3% (70/145), of which the complete response rate was 24.1%.
Moreover, 15.2% of patients are in stable condition.
The latest data show that the median duration of remission for patients reached 12.58
months, and the median duration of remission for the subgroup of patients who achieved
complete remission reached 13.37 months.
According to the 2019 report "Lymphoma Treatment Market Size, Share & Trends
Analysis Report By Type", the market size of DLBCL treatment drugs is expected to reach
nearly US$4.3 billion in 2022. In 2020, the global sales of Novartis Kymriahd were
US$473 million, higher than its revenue in 2019. At the same time, Gilead’s Yescarta has
global sales of US$563 million in 2020. With the approval of the ADC drug Zynlonta, it is

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expected that the enthusiasm for research and development in this field will continue to
increase.
References:
[1] ADC Therapeutics Announces FDA Approval of ZYNLONTA™(loncastuximab
tesirine-lpyl) in Relapsed or Refractory Diffuse Large B-CellLymphoma. Retrieved April 23,
2021, from https://www.businesswire.com/news/home/20210423005537/en
[2] ADC Therapeutics Corporate Presentation. Retrieved April23, 2021,
from https://s24.q4cdn.com/575174480/files/doc_presentations/2021/04/ADCT-Corporate
-Presentation-April-2021-v3-(optimized).pdf
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