FDA Receives BLA for Lonca in Relapsed/Refractory Diffuse Large B-cell Lymphoma

A Biologics License Application (BLA) was submitted to the FDA for loncastuximab tesirine (Lonca), an antibody-drug conjugate, as treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).¹

“The completion of our first BLA submission to the FDA is a significant milestone for ADC Therapeutics and takes us one step further in our evolution toward becoming a commercial-stage organization,” said Chris Martin, chief executive officer of ADC Therapeutics, in a statement.

The BLA was supported by results from the phase 2 LOTIS 2 study, which assessed the safety and efficacy loncastuximab tesirine in relapsed/refractory DLBCL following 2 or more prior lines of therapy.

LOTIS enrolled 145 patients who had a median of 3 prior lines of therapy (range, 2-7). The histologies associated with the study population were high-grade B-cell lymphoma with MYC and BCL2 and/or BLC6 rearrangements (11.0%), primary mediastinal B-cell lymphoma (4.1%), and transformed indolent lymphoma (17.9%). Disease was stage IV in 63.4% of the patients enrolled. Patients had a median age of 66 years (range, 23-94). DLBCL not otherwise specified was observed in 84.8% of patients. There were some patients who had received stem cell transplantation (16.6%). It was noted that 20.0% of patients were primary refractory to their most recent therapy and 56.5% were refractory.^1,2

All patients in the study received a median of 3 cycles (range, 1-10) of loncastuximab tesirine.

Patients were evaluated for the primary end point of overall response rate (ORR). In addition, patients were evaluated for duration of response (DOR), complete response (CR) rate, relapsed-free survival, progression-free survival, overall survival, and the frequency and severity of adverse events (AEs), as well as serious AEs as key secondary end points.

Treatment with loncastuximab tesirine led to an ORR of 48.3% with CRs observed in 24.1% of patients.

Overall, the drug appeared tolerable. The most common treatment-emergent AEs observed in the study occurring in ≥10% were neutropenia (25.5%), thrombocytopenia (17.9%), gamma-glutamyl transferase increased (16.6%), and anemia (10.3%). Among patients who experienced neutropenia, there was also a low incidence of febrile neutropenia (3.4%).

“A critical unmet need remains for heavily pretreated patients with relapsed or refractory DLBCL, including those with a poor prognosis, those who never responded to prior therapy and those who received prior stem cell transplant,” stated Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics. “Based on the anti-tumor activity, durability and generally manageable tolerability Lonca has demonstrated in LOTIS 2, we believe Lonca has the potential to fill this need.”

The phase 2 multicenter, open-label, single-arm clinical trial is ongoing but no longer recruiting patients. Those enrolled were required to be at least 18 years of age with a pathologic diagnosis of DLBCL according to the 2016 World Health Organization classification. Other requirements for enrollment included relapsed/refractory disease, measurable disease, available tumor tissue, an ECOG performance status of 0 to 2, and adequate organ function.

Individuals were ineligible to enroll if they had prior treatment with loncastuximab tesirine, known history of hypersensitivity to serum human ADA, a pathologic diagnosis of Burkitt lymphoma, and had undergone prior treatment that may have interfered with the study treatment.

Currently, another study of loncastuximab tesirine (LOTIS 5, NCT04384484), which is pivotal phase 2 clinical trial in patients with relapsed/refractory DLBCL. The drug is also being evaluated in combination with ibrutinib (Imbruvica) in both patients with DLBCL and mantle cell lymphoma, in the LOTIS 3 clinical trial (NCT03684694).

_References:

_{1. ADC Therapeutics submits Biologics License Application to the U.S. Food and Drug Administration for loncastuximab tesirine for treatment of relapsed or refractory diffuse large b-cell lymphoma. News release. September 21, 2020. Accessed September 21, 2020. https://bit.ly/2RQpm4I​}

_{2. Carlo-Stella C, Zinzani PL, Kahl B, et al. Initial results of a phase 2 study of loncastuximab tesirine, a novel pyrrolobenzodiazepine-based antibody-drug conjugate, in patients with relapsed or refractory diffuse large b-cell lymphoma. EHA Library. 2020; 2 95053; S233}