DS-3939a, a novel antibody–drug conjugate (ADC), is emerging as a promising treatment for advanced prostate cancer and other cancers where tumor-associated MUC1 (TA-MUC1) is overexpressed.
TA-MUC1, a glycoprotein found in about 90% of advanced prostate cancer cases with lymph node metastases, is a key driver of tumor progression, invasion, and immune evasion due to its aberrant glycosylation.
This makes it an ideal target for precision therapies like DS-3939a, which leverages DXd ADC technology to deliver a potent cytotoxic payload directly to cancer cells.
The design of DS-3939a includes a humanized anti-TA-MUC1 antibody (gatipotuzumab), a tetrapeptide-based cleavable linker, and a DXd payload, an exatecan derivative that inhibits DNA topoisomerase I.

The antibody binds specifically to TA-MUC1’s tumor-specific glycoforms, which are minimally expressed in healthy tissues, ensuring targeted delivery.

Preclinical studies have demonstrated its efficacy, showing significant tumor regression in TA-MUC1-positive prostate cancer models and other cancers like bladder and lung, with no effect on TA-MUC1-negative cells, underscoring its specificity.In advanced prostate cancer, TA-MUC1’s high expression, particularly in metastatic cases with higher Gleason scores, correlates with aggressive disease and poor prognosis.

The ADC is currently under evaluation in a phase 1/2 clinical trial, which began dosing patients across Asia, North America and Europe in September 2023.

Clinical trial.

Source.