The National Comprehensive Cancer Network has added loncastuximab tesirine-lpyl to the NCCN Clinical Practice Guidelines in oncology for B-cell lymphomas.
The National Comprehensive Cancer Network (NCCN) has added loncastuximab tesirine-lpyl (Lonca; Zynlonta) to the NCCN Clinical Practice Guidelines in oncology for B-cell lymphomas, according to a press release by ADC Therapeutics.
The guidelines now include the agent as a category 2A treatment option for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after 2 or more lines of systemic therapy. Lonca is a CD19-directed antibody drug conjugate. After the agent is internalized by CD19-expressing cells, a pyrrolobenzodiazepine payload. The payloads bind to DNA minor groove with little distortion, making the groove less visible to DNA repair mechanisms. This results in cell cycle arrest and the death of the tumor cell.
Lonca was granted an accelerated approval for the treatment of relapsed or refractory large B-cell lymphoma after 2 or more lines of therapy, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. Continued approval may be based upon verification and description of clinical benefit in a confirmatory clinical trial. The agent is also being evaluated in combination studies on other B-cell malignancies and earlier therapy lines.
“We were pleased to learn that less than two weeks after accelerated FDA approval, Zynlonta was added to the NCCN treatment guidelines with a category 2A recommendation,” said Chris Martin, chief executive officer of ADC Therapeutics in a press release. “Inclusion in the NCCN treatment guidelines highlights the high unmet medical need for a differentiated, targeted therapy in relapsed and refractory diffuse large B-cell lymphoma.”
The accelerated approval of lonca was based upon the results of the phase 2 LOTIS-2 trial (NCT03589469). The single-group assignment study had an actual enrollment of 145 participants. The primary endpoint of the study was overall response rate (ORR). Secondary outcomes include duration of response (DOR), complete response rate (CR), relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS), frequency and severity of adverse events (AEs) and serious AEs, and time to maximum concentration.
The study consisted of a single arm, where patients received lonca as an IV infusion over 30 minutes on the first day of each 3-week cycle at a dose of 150 μg/kg every 3 weeks (Q3W) for 2 cycles, then 75 μg/kg Q3W for subsequent cycles. Patients received therapy up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.
In order to participate, patients must be 18 years old or older with a pathologic diagnosis of DLBCL. Additionally, disease must be relapsed or refractory following 2 or more multi-agent systemic treatment regimens. Patients who have had previous CD19-directed therapy must have a biopsy showing CD19 protein expression after completion of the therapy. Patients who have had previous treatment with lonca, a known history of hypersensitivity to or positive serum human adenosine deaminase to a CD19 antibody, or pathologic diagnosis of Burkitt lymphoma were not eligible to participate.
Patient in the study were followed for a median of 7.3 months. The ORR observed with lonca 48.3% (95% CI, 39.9-56.7) and the CR was 24.1% (95% CI, 17.4-31.9). The median DOR was 10.3 months (95% CI, 6.9-NE). The most common AE after receiving the agent was laboratory abnormalities, thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, and anemia.2
“The rapid inclusion of Zynlonta in the NCCN guidelines reinforces our work on behalf of patients who have been heavily pretreated and have difficult-to-treat disease,” said Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics, in the press release. “Importantly, there is a broad range of pretreated patients needing new therapies, including those who are transplant eligible and ineligible, and patients who previously received stem cell transplant or [chimeric antigen receptor]-T cell therapy.”