non-Hodgkin lymphoma

Seattle Genetics has started a Phase I clinical trial of SGN-CD19B, a new antibody-drug conjugate (ADC) for relapsed or refractory patients with B-cell non-Hodgkin lymphoma (NHL).

The trial is for patients with two subtypes of B-cell NHL: diffuse large B-cell lymphoma (DLBCL) and grade 3 follicular lymphoma.

CD19 is a protein expressed broadly on normal and malignant B-cells.

SGN-CD19B is composed of an anti-CD19 antibody attached to a pyrrolobenzodiazepine (PBD) dimer, which is a highly potent cytotoxic DNA-crosslinking agent.

The Phase I trial is designed to evaluate the safety and anti-tumour activity of SGN-CD19B.

Seattle Genetics Research and Development executive vice-president and chief medical officer Jonathan Drachman said: "B-cell malignancies are the most common type of non-Hodgkin lymphoma, or NHL. In the relapsed or refractory disease setting, B-cell NHL is difficult to treat, and there is an urgent need to identify more effective treatment options for these patients.

"With SGN-CD19A and SGN-CD19B, we are evaluating two clinical-stage ADCs directed against CD19 utilising different ADC technologies with distinct mechanisms of action, which may result in differentiated clinical profiles and utility in NHL.

"Together with Adcetris, these programmes are a part of our extensive efforts to improve outcomes for patients with lymphoma."

"These programmes are a part of our extensive efforts to improve outcomes for patients with lymphoma."

The trial’s primary endpoints are the estimation of the maximum tolerated dose and evaluation of the safety of SGN-CD19B.

It will also assess antitumour activity, pharmacokinetics, objective response rate and progression-free survival.

Around 100 relapsed or refractory patients will be enrolled in the trial at multiple US centres, and administered SGN-CD19B every four to six weeks.

Preclinical data showed that SGN-CD19B exhibits antitumour activity against a broad panel of CD19-expressing B-cell malignancies, inducing durable tumour regressions in multiple preclinical models of NHL and B-ALL.

Image: Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Photo: courtesy of Nephron.