FDA Approves Lonca in Relapsed/Refractory DLBCL

The FDA has granted approval top loncastuximab tesirine (Lonca, Zynlonta) for the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), according to a press release from ADC Therapeutics.¹

Approval for Loncastuximab tesirine is based on the results of the phase 2 LOTIS-2 trial (NCT03589469), which showed that the agent elicited a high response rate in patients R/R DLBCL who have received 2 or more prior lines of therapy.¹

The LOTIS-2 trial enrolled 145 patients. The primary outcome of the study was overall response rate (ORR). Secondary outcomes included duration of response (DOR) up to 3 years, complete response (CR), relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS), frequency and severity of adverse events (AEs), and time to maximum concertation of Loncastuximab Tesirine, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199.

During the single-arm study, patients received the agent intravenously over 30 minutes on day 1 of each 3-week cycle at a dose of 150 μg/kg Q3W for 2 cycles. After that, patients received 75 μg/kg Q3W for every cycle up to one year after the initial treatment or until disease progression, unacceptable toxicity, or any other discontinuation criteria, whichever occurs first.

The overall ORR to the agent was 48.3%. In total, 24.1% of patients experienced a CR. The median age of the participants was 66 years. Patients had between 2 to 7 prior systemic therapies, with a median of 3. At least 1 post-baseline score was available for 130 patients. The completion rate among patients treated at each visit was 92% or higher. After 9 cycles of therapy, less than 20 patients had patient-reported outcome scores available for analysis.

In terms of tolerability, fatigue was the most reported symptoms at baseline, with 34% to 59% of patients reporting ‘somewhat’ to ‘very much’). Additionally, 80% or more of patients reported they had no, or a little bit of fever, night sweats, losing, weight, itching, and loss of appetite at baseline. Grade 3 AEs or higher occurred in 10% or more of patients, the most common being neutropenia (25.5%) and thrombocytopenia (17.9%). ²

In order to participate, patients were required to be 18 years of age older with a pathologic diagnosis of DLBCL. Patients also must have R/R disease following 2 or more multi-agent systemic treatment regimens and adequate organ function. Patients who have had previous treatment with loncastuximab tesirine, a known history of hypersensitivity to or positive serum human ADA to a CD19 antibody, or a pathologic diagnosis of Burkitt lymphoma are not eligible to participate.

“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 Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center, and Case Comprehensive Cancer Center, Case Western Reserve University in a press release. “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.”

A confirmatory phase 3 trial, LOTIS-5 (NCT04384484) is planned to test the agent against standard immunochemotherapy. It aims to enroll 350 patients with R/R DLBCL.

_REFERENCE:

_{1.ADC Therapeutics nnounces FDA pproval of ZYNLONTA™ (loncastuximab tesirine-lpyl) in relapsed or refractory diffuse large B-Cell lymphoma. News release. April 23, 2021. Accessed April 23, 2021. https://bit.ly/3gy7J7t.}

_{2.Spira A, Chen L, Zhou X, et al. Symptoms, health-related quality of life, and tolerability of Loncastuximab Tesirine in patients with relapsed or refractory diffuse large B cell lymphoma. Blood 2020; 136 (Supplt 1): 3-4. doi: https://doi.org/10.1182/blood-2020-139571}