Accelerated Approval for Loncastuximab Tesirine-lpyl in DLBCL

The FDA on Friday granted accelerated approval to loncastuximab tesirine-lpyl, to be marketed as Zynlonta, for adult patients with relapsed or refractory large B-cell lymphoma after they have tried at least 2 other lines of systemic therapy.

Approval for the CD-19–directed antibody and alkylating agent conjugate covers patients being treated for diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma, according to a statement from the FDA.

ADC Therapeutics is the maker of loncastuximab tesirine-lpyl.

The approval was based on LOTIS-2, an open-label, single-arm trial that involved 145 adult patients with relapsed or refractory DLBCL or high-grade B-cell lymphoma, who had received at least 2 prior systemic regimens. Patients received loncastuximab tesirine-lpyl 0.15 mg/kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks. Patients were treated until their disease progressed or they experienced unacceptable toxicity.

Almost half the patients had some response to treatment, with an overall response rate (ORR) of 48%, as measured by an independent review committee (95% CI, 39.9%-56.7%). Nearly a quarter of patients (24.1%) had a complete response rate (95% CI, 17.4%-31.9%). After a median follow-up of 7.3 months, median response duration was 10.3 months (95% CI, 6.9–not estimable). According to the FDA statement, of the 70 patients who achieved objective responses, 36% were censored for response duration prior to 3 months.

The most common adverse reactions in patients receiving loncastuximab tesirine-lpyl—meaning they happened in at least 20% of patients—including laboratory abnormalities, were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

The prescribing information provides warnings and precautions for adverse reactions including edema and effusions, myelosuppression, infections, and cutaneous reactions. Patients should be premedicated with dexamethasone 4 mg orally or intravenously twice daily for 3 days beginning the day before loncastuximab tesirine-lpyl.

“The FDA approval of Zynlonta is an exciting advancement for patients with r/r DLBCL and a transformational event for ADC Therapeutics,” Chris Martin, the company’s CEO, said in a statement. “We extend our deepest gratitude to the patients who participated in our LOTIS-1 and LOTIS-2 clinical trials, their families, the study investigators and our employees, as their commitment made this important milestone possible.”