General Information

Zynlonta (loncastuximab tesirine-lpyl) is a CD19-directed antibody and alkylating agent conjugate.

Zynlonta is specifically 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.

Zynlonta is supplied as an injection for intravenous administration. Zynlonta intravenous infusion is administered over 30 minutes on Day 1 of each cycle (every 3 weeks). Administer intravenous infusion as follows:

• 0.15 mg/kg every 3 weeks for 2 cycles.
• 0.075 mg/kg every 3 weeks for subsequent cycles

Mechanism of Action

Zynlonta (loncastuximab tesirine-lpyl) is an antibody-drug conjugate (ADC) targeting CD19. The monoclonal IgG1 kappa antibody component binds to human CD19, a transmembrane protein expressed on the surface of cells of B-lineage origin. The small molecule component is SG3199, a PBD dimer and alkylating agent. Upon binding to CD19, loncastuximab tesirine-lpyl is internalized followed by release of SG3199 via proteolytic cleavage. The released SG3199 binds to the DNA minor groove and forms highly cytotoxic DNA interstrand crosslinks, subsequently inducing cell death. Loncastuximab tesirine-lpyl had anticancer activity in animal models of lymphoma.

Side Effects

Adverse effects associated with the use of Zynlonta may include, but are not limited to, the following:

• thrombocytopenia
• increased gamma-glutamyltransferase
• neutropenia
• anemia
• hyperglycemia
• transaminase elevation
• fatigue
• hypoalbuminemia
• rash
• edema
• nausea
• musculoskeletal pain

Clinical Trial Results

The FDA granted accelerated approval for Zynlonta for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of Zynlonta for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145 patients), which included a complete response (CR) rate of 24.1% and a partial response (PR) rate of 24.1%. Patients had a median time to response of 1.3 months and the median duration of response (mDoR) for the 70 responders was 10.3 months (inclusive of patients who were censored).