Date: 2014-12-18
Type of information: Initiation of the trial
phase: 1b
Announcement: initiation of the trial
Company: Seattle Genetics (USA - WA)
Product: SGN-CD33A in combination with standard of care chemotherapy, including cytarabine and daunorubicin
Action
mechanism: antibody drug conjugate. SGN-CD33A is a novel antibody drug conjugate (ADC) targeted to CD33 utilizing Seattle Genetics’ newest technology. CD33 is expressed on most AML cells regardless of subtype, cytogenetic abnormality or underlying mutational heterogeneity. SGN-CD33A is the first ADC utilizing an engineered cysteine antibody (EC-mAb) and pyrrolobenzodiazepine (PBD) dimer to be advanced into the clinic. SGN-CD33A is comprised of three parts: A cysteine-engineered anti-CD33 antibody enabling uniform site-specific conjugation, a cleavable dipeptide linker that is highly stable in circulation, and a PBD dimer that binds DNA with high intrinsic affinity. PBD dimers are a class of DNA-crosslinking agents significantly more potent than systemic chemotherapeutic drugs. SGN-CD33A employs a novel linker system and proprietary, site-specific conjugation technology (EC-mAb) that 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 cytotoxic agent upon internalization into CD33-expressing cells.
Disease: acute myeloid leukemia
Therapeutic area: Cancer - Oncology
Country: USA
Trial details:
Latest
news: * On December 18, 2014, Seattle Genetics announced initiation of a phase 1b clinical trial of SGN-CD33A in combination with standard of care chemotherapy, including cytarabine and daunorubicin, for patients with newly diagnosed acute myeloid leukemia (AML). The trial will also evaluate SGN-CD33A in the consolidation setting for AML, both in combination with cytarabine and as a single-agent maintenance regimen. The study is a phase 1b, open-label, multi-center, dose-escalation clinical trial designed to evaluate SGN-CD33A administered in combination with frontline standard of care regimens for induction (cytarabine and daunorubicin) and/or consolidation (cytarabine). In addition, the study will evaluate single-agent SGN-CD33A as a maintenance regimen. The primary endpoints are determination of the maximum tolerated dose and safety profile of SGN-CD33A in these settings. In addition, the trial will evaluate anti-leukemic activity, pharmacokinetics, progression-free survival and overall survival. The phase 1b trial will enroll approximately 90 patients at multiple centers in the United States. Clinical data from an ongoing phase 1 trial of SGN-CD33A in AML were presented in an oral session at the 2014 American Society of Hematology (ASH) Annual Meeting (Abstract #623). In this dose-escalation study, 56 patients had been enrolled. Patients were primarily older (median age 75 years) with relapsed AML, predominantly with intermediate or adverse cytogenetic risk and 55 percent had underlying myelodysplasia. Single-agent SGN-CD33A induced bone marrow blast clearance in 44 percent of evaluable patients treated across all dose levels, including 21 percent with a complete remission or complete remission with incomplete recovery (CR/CRi). A dose-response relationship is evolving, with 77 percent of patients treated at doses greater than or equal to 40 micrograms per kilogram achieving at least 50 percent blast reduction. Adverse events were generally manageable and associated with underlying myelosuppression.
