Antibody-drug conjugates represent an innovative and important therapeutic approach to targeting cancer. Seattle Genetics ( 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.