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DCLL9718S + azacitidine
- Development stage
- Unknown
- Lead developer
- Genentech
- Modality
- Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
DCLL9718S + azacitidine is an investigational combination therapy being studied for the treatment of acute myeloid leukemia (AML). DCLL9718S is a THIOMAB antibody-drug conjugate (ADC) that combines a humanized monoclonal IgG1 anti-CLL1 antibody (MCLL0517A) linked to two pyrrolobenzodiazepine (PBD) dimer drugs via a cleavable disulfide linker. The antibody binds to C-type lectin-like molecule 1 (CLL1) on target cells, leading to internalization, lysosomal degradation, and release of the cytotoxic PBD dimer, which causes DNA cross-linking and cell death. Azacitidine is a hypomethylating agent that inhibits DNA methyltransferase, promoting DNA hypomethylation and cell differentiation or apoptosis. The combination is studied primarily in patients with previously untreated AML who are unsuitable for intensive induction chemotherapy. Clinical development has focused on safety, tolerability, and preliminary efficacy, with trials indicating limited tolerability and no objective responses for DCLL9718S as monotherapy.
- Other names
- DCLL-9718S + azacitidine
02
Targets
DNADNMT (DNA methyltransferase)CLEC12A
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