About 85 percent of NHL is of B-cell lineage, and CD19 is broadly expressed across all subtypes of B-cell malignancies. SGN-CD19B is a novel antibody-drug conjugate (ADC) targeted to CD19 utilizing Seattle Genetics’ newest ADC technology.
SGN-CD19B is composed of an anti-CD19 antibody attached to a highly potent cytotoxic DNA-crosslinking agent called a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). The trial is designed to assess the safety and antitumor activity of SGN-CD19B.
"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," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics.
"With SGN-CD19A and SGN-CD19B, we are evaluating two clinical-stage ADCs directed against CD19 utilizing different ADC technologies with distinct mechanisms of action, which may result in differentiated clinical profiles and utility in NHL. Together with ADCETRIS, these programs are a part of our extensive efforts to improve outcomes for patients with lymphoma."
The study is a phase 1, open-label, multi-center, dose-escalation clinical trial. The primary endpoints are the estimation of the maximum tolerated dose and evaluation of the safety of SGN-CD19B. In addition, the trial will evaluate antitumor activity, pharmacokinetics, objective response rate and progression-free survival. The study is designed to evaluate SGN-CD19B administered every four or six weeks and will enroll up to approximately 100 relapsed or refractory patients at multiple centers in the United States.
Preclinical data presented at the 2015 American Society of Hematology (ASH) Annual Meeting demonstrated that SGN-CD19B exhibits antitumor activity against a broad panel of CD19-expressing B-cell malignancies, inducing durable tumor regressions in multiple preclinical models of NHL and B-ALL.
With more than 15 years of experience and innovation, Seattle Genetics is the leader in developing ADCs. ADCs are monoclonal antibodies that are designed to selectively deliver cell-killing agents to tumor cells. This approach is intended to spare non-targeted cells and, thus, reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.