FDA Approves Zynlonta for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

The antibody drug conjugate Zynlonta (loncastuximab tesirine-lpyl) has been granted an approval by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to ADC Therapeutics, the manufacturer of the drug.

This approval addresses an unmet need across a broad population of third-line relapsed or refractory patients, including patients with DLBCL not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.

“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 Dr. Paolo F. Caimi, of University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center and Case Western Reserve University. “Single-agent Zylonta 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 approval was based on the results of the phase 2 multi-center, open-label, single-arm LOTIS 2 clinical trial, which evaluated the efficacy and safety of Zynlonta in patients with relapsed or refractory DLBCL following two or more lines of prior therapy.

The 145 patients enrolled in this trial received 30-minute intravenous infusions of Zynlonta once every three weeks at a dose of 150 μg/kg for the first two cycles, followed by 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurred first.

As of the data cut-off date of April 6, 2020, 145 patients who had received a median of three prior lines of therapy were enrolled and had received a mean of 4.3 cycles of Zynlonta.

Zynlonta demonstrated an overall response rate (ORR) of 48.3% and a complete response (CR) rate of 24.1%, exceeding the study’s target primary endpoint of ORR. Additionally, patients who were refractory to first-line or last-line prior therapy had ORRs of 37.9% and 36.9%, respectively. Compared to a previous data readout in October 2019, the median duration of response increased from 6.7 months to 10.25 months.

The most common grade 3 or higher treatment-emergent adverse events were thrombocytopenia, elevated levels of two specific types of enzymes commonly found in the liver (gamma-glutamyl transferase and transaminase), neutropenia, anemia, hyperglycemia, fatigue, low levels of albumin in the blood, rash, swelling, nausea and musculoskeletal pain.

“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, the chief executive officer 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.”

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