Investigational Drug Shows Promise in Diffuse Large B-Cell Lymphoma


A new investigational drug called ADCT-402 that combines a cell-killing compound with a monoclonal antibody shows early promise for patients with diffuse large B-cell lymphoma.

A new investigational drug called ADCT-402 (loncastuximab tesirine) that combines a cell-killing compound with a monoclonal antibody shows early promise for patients with diffuse large B-cell lymphoma (DLBCL). The complete response rate was almost 40%, according to results of a study published in Clinical Cancer Research.

DLBCL is the most common aggressive subtype of non-Hodgkin lymphoma and accounts for about a third of all newly diagnosed cases. First-line treatments cure 60% to 70% of patients. Many more may respond to stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy. But for the group that still doesn’t respond to those options, few if any choices remain.

“With most of the established treatments, we typically see response rates around 30% for DLBCL patients,” said study author Brad S. Kahl, a medical oncologist at Washington University in St. Louis School of Medicine in Missouri. “To have a therapy with a higher response rate and some durability would be a great advancement for the field and for these patients.”

The goal was to report on the safety, tolerability, pharmacokinetic (PK) profile, and the preliminary clinical activity in a dose-escalation part of the phase I study, according to the paper.

The single-arm, open-label trial involved 12 international centers and incorporated 88 patients who had relapsed or refractory B-cell non-Hodgkin lymphoma. Sixty-three of these patients were diagnosed with DLBCL. All had failed, or were intolerant to, the established therapies, according to the findings.

The patients were administered the ADCT-402 intravenously every 3 weeks, the protocols stated. The patients who fared best with their disease were administered the greatest doses. The highest level was 120 micrograms of the drug per kilogram of body weight or greater, according to the investigators.

Of the 51 patients with DLBCL who were treated at or above this dosage threshold, 37.3% had a complete response, and 17.6% had a partial response. Of the total patient group, 40.6% had a complete response, and 18.8% had a partial, the authors concluded.  

Nearly three-quarters of the patients (65 of 88, 73.9%) reported an adverse event of grade 3 or higher, with the most common being decreased platelet or neutrophil counts, and fatigue, among other effects.

“Loncastuximab tesirine had promising activity with acceptable safety in this dose-escalation study,” the authors concluded, adding that a phase II study at the 150 microgram/kilogram level has been started already.

“There is a large unmet need for patients with relapsed/refractory DLBCL, particularly for patients who don’t respond to stem cell transplant or CAR T,” said Kahl. “There are really no attractive options currently available for those patients… We’re hopeful that ADCT-402 will ultimately prove to be a good addition for this patient population.” 

Kahl B, Hamadani M, Radford J, et al. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2019. Published Online November 4, 2019. DOI: 10.1158/1078-0432.CCR-19-0711.

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