ADC Therapeutics announced that the US Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and high-grade B-cell lymphoma. ZYNLONTA, a CD19-targeted antibody-drug conjugate (ADC), has been granted accelerated approval by the FDA based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Paolo F Caimi, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University said, “Single-agent ZYNLONTA demonstrated clinically important outcomes in the pivotal LOTIS-2 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.”
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 per cent (70/145 patients), which included a complete response (CR) rate of 24.1 per cent (35/145 patients) and a partial response (PR) rate of 24.1 per cent (35/145 patients). 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). In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anaemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, oedema, 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%).
“The FDA approval of ZYNLONTA is an exciting advancement for patients with r/r DLBCL and a transformational event for ADC Therapeutics,” said Chris Martin, CEO of ADC Therapeutics. “We extend our deepest gratitude to the patients who participated in our LOTIS-1 and LOTIS-2 clinical trials, their families, the study investigators and our employees, as their commitment made this important milestone possible.”