The FDA has accepted and granted priority review to the biologics license application (BLA) for loncastuximab tesirine (Lonca) for the treatment of relapsed or refractory diffuse large B-cell lymphoma.
The FDA has accepted and granted priority review to the biologics license application (BLA) for loncastuximab tesirine (Lonca) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to ADC Therapeutics, the developer of the agent.1
A prescription drug user fee act (PDUFA) target action date has been set by the FDA for May 21, 2021.
“The FDA’s acceptance of our BLA and granting of priority review for Lonca is a tremendous accomplishment that brings ADC Therapeutics one step closer to being able to offer patients with relapsed or refractory DLBCL a greatly needed new treatment option in 2021,” Chris Martin, chief executive officer of ADC Therapeutics, said in a press release. “We look forward to working with the FDA during its review of our BLA submission for Lonca. Our organization remains focused on robust planning for a successful launch next year.”
The BLA submission was based on data from the pivotal phase 2 multi-center, open-label, single-arm LOTIS 2 clinical trial, evaluating the efficacy and safety of Lonca in patients with relapsed or refractory DLBCL following 2 or more lines of prior therapy. In June 2020, maturing data from LOTIS 2 was presented at the virtual 25th Congress of the European Hematology Association.2
Patients enrolled in the trial received 30-minute intravenous infusions of Lonca once every 3 weeks at a dose of 150 μg/kg for the first 2 cycles, followed by 75 μg/kg for subsequent cycles for up to 1 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 were enrolled and had received a mean of 4.3 cycles of Lonca (range, 1-15).
Of note, patients had received a median of 3 prior lines of therapy.
Lonca demonstrated an overall response rate (ORR) of 48.3% and a complete response (CR) rate of 24.1%, compared toan ORR of 45.5% and CR rate of 20.0% reported in the previous data cut (October 14, 2019). This exceeded the study’s target primary end point of ORR.
Moreover, patients who were refractory to first-line or last-line prior therapy had ORRs of 37.9% and 36.9%, respectively. The median duration of response also increased to 10.25 months, compared to 6.7 months in the previous data cut.
The tolerability profile was manageable with the most common grade 3 or higher treatment-emergent adverse events observed being neutropenia (25.5%) with low incidence of febrile neutropenia (3.4%), thrombocytopenia (17.9%), gamma-glutamyl transferase (GGT) increase (16.6%), and anemia (10.3%).
Data from subgroup analyses of LOTIS 2 will also be presented in a poster at the upcoming 62nd American Society for Hematology (ASH) Annual Meeting.
Lonca is an antibody drug conjugate (ADC) composed of designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, therefore disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death. CD19 is a clinically validated target for the treatment of B-cell malignancies.
Lonca is also being evaluated in LOTIS 3, a phase 1/2 clinical trial in combination with ibrutinib (Imbruvica) in patients with relapsed or refractory DLBCL or mantle cell lymphoma, as well as LOTIS 5, a phase 3 confirmatory clinical trial in combination with rituximab (Rituxan) in patients with relapsed or refractory DLBCL.
1. ADC Therapeutics Announces FDA Accepts Biologics License Application and Grants Priority Review for Loncastuximab Tesirine for Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma [news release]. Lausanne, Switzerland. Published November 20, 2020. Accessed November 20, 2020. https://ir.adctherapeutics.com/press-releases/press-release-details/2020/ADC-Therapeutics-Announces-FDA-Accepts-Biologics-License-Application-and-Grants-Priority-Review-for-Loncastuximab-Tesirine-for-Treatment-of-Relapsed-or-Refractory-Diffuse-Large-B-cell-Lymphoma/default.aspx
2. ADC Therapeutics Announces Maturing Data from Pivotal Phase 2 Clinical Trial and Phase 1/2 Combination Clinical Trial of Loncastuximab Tesirine (Lonca) in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma [news release]. Lausanne, Switzerland. Published June 12, 2020. Accessed November 20, 2020. https://www.businesswire.com/news/home/20200611005918/en/ADC-Therapeutics-Announces-Maturing-Data-from-Pivotal-Phase-2-Clinical-Trial-and-Phase-12-Combination-Clinical-Trial-of-Loncastuximab-Tesirine-Lonca-in-Patients-with-Relapsed-or-Refractory-Diffuse-Large-B-cell-Lymphoma