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Data updated: Jun 28, 2026

ZYNLONTA (loncastuximab tesirine-lpyl) · ADC Therapeutics SA

Genetic Support
Oncology Approved 2021-04-23

Zynlonta (loncastuximab tesirine-lpyl) is a CD19-directed antibody-drug conjugate indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. It is used after patients have undergone at least two lines of systemic therapy. The indication includes specific subtypes such as diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. This drug received accelerated approval based on overall response rate, and continued approval may depend on the verification of clinical benefit in confirmatory trials.

How ZYNLONTA Works

Loncastuximab tesirine-lpyl is an antibody-drug conjugate that targets CD19, a protein found on the surface of B-lineage cells. After binding to CD19, the agent is internalized into the cell, where it releases a small molecule alkylating agent called SG3199 via proteolytic cleavage. SG3199 then binds to the DNA minor groove and forms highly cytotoxic interstrand crosslinks. This process disrupts the DNA and subsequently induces cell death in the targeted lymphoma cells.

1
Indication
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Phase 3 Trials
1
Priority Reviews
5
Years on Market

Details

Status
Prescription
First Approved
2021-04-23
Patent Cliff
2028

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Routes
INJECTION
Dosage Forms
INJECTABLE

Companies

Active Ingredient: LONCASTUXIMAB TESIRINE-LPYL

ZYNLONTA Approval History

2022
2023
2024
2025
2026
Original
New Indication
New Form
Label Update
5 FDA actions from 2021 to 2026
Feb 2026 SUPPL
Label · Labeling
Jan 2026 SUPPL
Label · Labeling
Oct 2022 SUPPL
Label · Labeling

What ZYNLONTA Treats

3 indications

ZYNLONTA is approved for 3 conditions since its original approval in 2021. These indications span multiple therapeutic areas including oncology, immunology, and more.

Source: FDA Label

ZYNLONTA Target & Pathway

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Target

CD19 (B-Lymphocyte Antigen CD19) Cell Surface Marker

A protein expressed on B-cells throughout their development. CD19 is a key target for CAR-T cell therapies in B-cell leukemias and lymphomas, where engineered T-cells are directed to kill CD19-expressing cancer cells.

ZYNLONTA Competitive Set

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Three rings of competition based on shared molecular targets and treated indications.

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Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.

What's emerging in ZYNLONTA's indications

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Phase 3 candidates targeting molecules with no FDA-approved drug, in indications ZYNLONTA treats. First-in-class if their pivotal trials read out positive.

Drugs Similar to ZYNLONTA

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ADCETRIS
BRENTUXIMAB VEDOTIN
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SEATTLE GENETICS
Shared indications:
Large B-Cell LymphomaDiffuse Large B-Cell LymphomaHigh-Grade B-Cell Lymphoma
Breyanzi
lisocabtagene maraleucel
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Juno Therapeutics, Inc. a Bristol Myer-Squibb Company
Shared indications:
Large B-Cell LymphomaDiffuse Large B-Cell LymphomaHigh-Grade B-Cell Lymphoma
EPKINLY
EPCORITAMAB-BYSP
2 shared
GENMAB US, INC.
Shared indications:
Diffuse Large B-Cell LymphomaHigh-Grade B-Cell Lymphoma
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Active Pipeline

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Key Completed Trials

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Completed studies with published results, ranked by significance

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Trial Timeline

Full development history with FDA approval milestones

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Understanding FDA Approval Types
Count Type What it means
- ORIG Original approval - drug first enters market
- SUPPL - Efficacy New indication (new disease/condition approved)
- SUPPL - Labeling Label text changes (warnings, dosing updates)
- SUPPL - Manufacturing Production changes (new facility)
- SUPPL - Chemistry Formulation changes (new dosage strength)

Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.

ZYNLONTA FDA Label Details

Indications & Usage

FDA Label (PDF)

ZYNLONTA is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more 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. This indication is approved under accelerated approval based on overall response rate [see Clinical Studies ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ZYNLONTA is a CD19-directed antibody and alkylating ...

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Data Sources

Data sourced from official FDA and NIH databases. Click links to verify on original sources.