The submission is based on results from the phase 2 LOTIS 2 clinical trial, which is evaluating the efficacy and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL following at least 2 lines of prior systemic therapy.
ADC Therapeutics announced the submission of a biologics license application (BLA) to the FDA for loncastuximab tesirine (Lonca) for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The BLA submission is based on results from the pivotal, multicenter, open-label, single-arm, phase 2 LOTIS 2 clinical trial, which is evaluating the efficacy and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL following at least 2 lines of prior systemic therapy.
“The completion of our first BLA submission to the FDA is a significant milestone for ADC Therapeutics and takes us one step further in our evolution toward becoming a commercial-stage organization,” Chris Martin, chief executive officer of ADC Therapeutics, said in a press release. “We are grateful to the trial participants and investigators and to all our employees for their commitment to this clinical program, and we look forward to working with the FDA to bring [loncastuximab tesirine] to patients as quickly as possible.”
In June 2020, maturing data from the LOTIS 2 trial was presented at the virtual 25th Congress of the European Hematology Association. As of the data cut-off date of April 6, 2020, 145 patients had been enrolled in the trial and had received a median of 3 prior lines of therapy.
Loncastuximab tesirine demonstrated an overall response rate of 48.3% (70/145 patients), exceeding the target primary end point, as well as a complete response rate of 24.1% (35/145 patients). Additionally, the tolerability profile was generally manageable, with the most common grade 3 or higher treatment-emergent adverse events (AEs) observed in at least 10% of patients being neutropenia (25.5%) with low incidence of febrile neutropenia (3.4%), thrombocytopenia (17.9%), increased gamma-glutamyl transferase (GGT) (16.6%), and anemia (10.3%).
“A critical unmet need remains for heavily pretreated patients with relapsed or refractory DLBCL, including those with a poor prognosis, those who never responded to prior therapy and those who received prior stem cell transplant,” Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics, said in the release. “Based on the anti-tumor activity, durability and generally manageable tolerability [loncastuximab tesirine] has demonstrated in LOTIS 2, we believe [loncastuximab tesirine] has the potential to fill this need.”
Notably, in addition to LOTIS 2, loncastuximab tesirine is being evaluated in Lotis 3, a phase 1/2 trial in combination with ibrutinib (Imbruvica) in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL), and LOTIS 5, a phase 3 confirmatory clinical trial in combination with rituximab (Rituxan) in patients with relapsed or refractory DLBCL.
ADC Therapeutics Submits Biologics License Application to the U.S. Food and Drug Administration for Loncastuximab Tesirine for Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma [news release]. Lausanne, Switzerland. Published September 21, 2020. Accessed September 23, 2020. https://ir.adctherapeutics.com/press-releases/press-release-details/2020/ADC-Therapeutics-Submits-Biologics-License-Application-to-the-U.S.-Food-and-Drug-Administration-for-Loncastuximab-Tesirine-for-Treatment-of-Relapsed-or-Refractory-Diffuse-Large-B-cell-Lymphoma/default.aspx