Loncastuximab tesirine appeared effective and safe for patients with relapsed or refractory diffuse large B-cell lymphoma, according to topline data released by the agent’s manufacturer.
Loncastuximab tesirine (ADCT-402, ADC Therapeutics) is an antibody-drug conjugate composed of a humanized monoclonal antibody directed against CD19 and conjugated to a pyrrolobenzodiazepine dimer cytotoxin.
A phase 2 trial designed to evaluate single-agent loncastuximab tesirine included 145 patients with relapsed or refractory DLBCL.
Patients received 30-minute IV infusions of loncastuximab tesirine every 3 weeks. They received 150 g/kg in the first two cycles, and 75 g/kg in subsequent cycles.
Treatment continued for up to 1 year or until disease progression, unacceptable toxicity or discontinuation.
Overall response rate served as the primary endpoint.
Researchers reported a 45% ORR, exceeding the primary endpoint target. Twenty percent of patients achieved complete response and 25.5% achieved partial response.
The agent’s toxicity profile appeared manageable, according to researchers. The most common grade 3 or higher treatment-emergent adverse events included neutropenia, thrombocytopenia and increased gamma-glutamyltransferase.
“These data exceeded our primary endpoint target and reinforce the significant single-agent antitumor activity and manageable toxicity profile of loncastuximab tesirine in patients with relapsed or refractory DLBCL who have failed established therapies,” Jay Feingold, MD, PhD, senior vice president and chief medical officer at ADC Therapeutics, said in a company-issued press release. “Loncastuximab tesirine has demonstrated its potential to fill a critical unmet need for a new therapy and become a key part of the treatment paradigm for all heavily pretreated patients with DLBCL. We plan to present final data from the pivotal phase 2 clinical trial at a future scientific meeting.”
Healio will continue to follow this trial and publish more detailed results when they are released, either through presentation at a scientific meeting or publication in a peer-reviewed journal.
ADC Therapeutics officials expect to submit a biologics license application that seeks accelerated approval of loncastuximab tesirine for this indication in the third quarter of this year.
A phase 1b trial is underway to evaluate the agent in combination with ibrutinib (Imbruvica; Janssen, Pharmacyclics) for patients with relapsed or refractory DLBCL or mantle cell lymphoma. Another phase 1b trial is evaluating the agent in combination with durvalumab (Imfinzi, AstraZeneca) for treatment of relapsed or refractory DLBCL, mantle cell lymphoma and follicular lymphoma.
The FDA previously granted orphan drug designation to loncastuximab tesirine for treatment of relapsed or refractory DLBCL and mantle cell lymphoma.
The FDA Office of Orphan Products Development grants orphan drug designation to novel drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. The designation allows manufacturers to qualify for various incentives, including tax credits for qualified clinical trials and — upon regulatory approval — 7 years of market exclusivity.