Antibody-drug conjugates represent an innovative and important therapeutic approach to targeting cancer. Seattle Genetics (www.seattlegenetics.com) announced that multiple abstracts will be presented in December at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, California, highlighting:

  • clinical trial results of phase 3 AETHERA clinical trial results for ADCETRIS (brentuximab vedotin) as consolidation therapy immediately following an autologous stem cell transplant (ASCT) in Hodgkin lymphoma (HL) patients at risk of relapse;
  • multiple presentations of ADCETRIS data in CD30-positive lymphomas, including frontline, salvage and relapsed HL, as well as diffuse large B-cell lymphoma (DLBCL) and cutaneous T-cell lymphoma (CTCL);
  • first interim clinical data for SGN-CD33A in acute myeloid leukemia (AML);
  • updated phase 1 clinical data to be presented for SGN-CD19A in acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL);
  • additional results from the phase 2 ROMULUS study assessing two ADC candidates that utilize Seattle Genetics’ proprietary technology being developed by Genentech: polatuzumab vedotin and pinatuzumab vedotin (ADCs targeting CD79b and CD22, respectively).

SGN-CD33A is a novel ADC targeted to CD33 utilizing Seattle Genetics’ newest ADC technology. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD33-expressing cells. SGN-CD19A is an ADC targeting CD19, a protein expressed broadly on B-cell malignancies. SGN-CD19A is comprised of an anti-CD19 monoclonal antibody linked to a synthetic cytotoxic cell-killing agent, monomethyl auristatin F (MMAF). The ADC is designed to be stable in the bloodstream, and to release its cytotoxic agent upon internalization into CD19-expressing tumor cells.