Read About ADC Therapeutics ZYNLONTA and Clinical Development

ZYNLONTA, whose active ingredient is loncastuximab tesirine-lpyl, is an antibody drug conjugate that targets CD19, a protein expressed on many B cells. The medicine combines an antibody component with a cytotoxic payload. After binding to CD19, the drug is taken into the target cell, where the payload interferes with DNA and can lead to cell death.

ZYNLONTA Approved Use and Treatment Approach

The U.S. Food and Drug Administration approved ZYNLONTA in 2021 for adults with relapsed or refractory large B cell lymphoma after two or more lines of systemic therapy. The approved population includes diffuse large B cell lymphoma not otherwise specified, DLBCL arising from low grade lymphoma, and high grade B cell lymphoma.

Important aspects of its clinical use include:

• ZYNLONTA is administered by intravenous infusion.
• Treatment is generally given once every three weeks according to the prescribed dosing schedule.
• Blood counts and liver function are monitored during treatment.
• Important risks include low blood cell counts, infections, liver problems, edema or fluid accumulation, and skin reactions.
• Common adverse effects reported in the prescribing information include fatigue, rash, swelling, nausea, musculoskeletal pain, and laboratory abnormalities.

The original approval was granted through the FDA accelerated approval pathway based on overall response rate, with continued approval dependent on verification and description of clinical benefit in confirmatory research.

Clinical Development and Ongoing Research

Clinical development of ZYNLONTA has expanded beyond its original single agent setting. LOTIS 5 is a Phase 3 confirmatory study evaluating ZYNLONTA in combination with rituximab for patients with relapsed or refractory DLBCL after one or more previous systemic treatments. In June 2026, ADC Therapeutics reported that the trial met its primary progression free survival endpoint. The reported median progression free survival was 6.1 months with ZYNLONTA plus rituximab compared with 4.7 months with the control regimen.

Other development activities include:

• LOTIS 7 is evaluating ZYNLONTA in combination with the bispecific antibody glofitamab in relapsed or refractory DLBCL.
• Enrollment in the selected dose group of LOTIS 7 was completed in June 2026, with full data expected later in 2026.
• Investigator initiated studies are evaluating ZYNLONTA with rituximab in relapsed or refractory follicular lymphoma.
• Additional research is examining ZYNLONTA as a potential treatment approach for marginal zone lymphoma.

The ongoing development of ZYNLONTA illustrates how antibody drug conjugates can be studied across different treatment settings and combinations. Clinical trials remain important for determining its potential role in additional B cell malignancies and treatment lines. The information presented here is educational and is not intended to provide medical advice, treatment recommendations, or sales and service information.