FDA Approves Novel Therapy for Relapsed or Refractory Diffuse Large B-cell Lymphoma

April 23, 2021

Loncastuximab tesirine-lpyl is a CD19-targeted antibody drug conjugate.

Officials with the FDA have approved ADC Therapeutics’ loncastuximab tesirine-lpyl (Zynlonta) for the treatment of certain adult patients with relapsed or refractory (R/R) large B-cell lymphoma after 2 or more lines of systemic therapy, according to the company. The drug is indicated for treatment of patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.

DLBCL, the most common type of non-Hodgkin lymphoma in the United States, is a rapidly progressing, aggressive disease that is heterogeneous with multiple subtypes. According to ADC Therapeutics, more than 40% of first-line DLBCL treatments fail. For patients who fail first-line therapy, prognoses are poor, worsening with each line of therapy as the chance for cure or long-term disease-free survival diminishes.

Loncastuximab tesirine-lpyl is a CD19-targeted antibody drug conjugate (ADC). The FDA granted accelerated approval based on overall response rate. According to ADC Therapeutics, continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ADC Therapeutics anticipates having loncastuximab tesirine-lpyl commercially available in the United States shortly.

“There is a significant unmet need for treatment options for patients with R/R DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease,” said Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University, in a prepared statement. “Single-agent [loncastuximab tesirine-lpyl] demonstrated clinically important outcomes in the pivotal LOTIS-2 [NCT03589469] study across several disease subtypes. Notably, this included transplant eligible and ineligible patients and patients who previously received stem cell transplant or CAR-T cell therapy.”

LOTIS-2 is a large (n=145) phase 2 multinational, single-arm clinical trial loncastuximab tesirine-lpyl for the treatment of adult patients with r/r DLBCL following 2 or more prior lines of systemic therapy. Results from the trial demonstrated an overall response rate of 48.3%, which included a complete response rate of 24.1%, and a partial response rate of 24.1%. Patients had a median time to response of 1.3 months and the median duration of response for the 70 responders was 10.3 months, inclusive of patients who were censored.

In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common (≥10%) grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

REFERENCE

ADC Therapeutics announces FDA approval of Zynlonta (loncastuximab tesirine-lpyl) in relapsed or refractory diffuse large B-cell lymphoma [news release]. April 23, 2021, ADC Therapeutics. Accessed April 23, 2021. https://ir.adctherapeutics.com/press-releases/press-release-details/2021/ADC-Therapeutics-Announces-FDA-Approval-of-ZYNLONTA-loncastuximab-tesirine-lpyl-in-Relapsed-or-Refractory-Diffuse-Large-B-Cell-Lymphoma/default.aspx