BG-C0979: Pioneering Phase 1 Trial Targets ADAM9 in Advanced Solid Tumors, Including CRPC

A first-in-human Phase 1 clinical trial is underway to evaluate BG-C0979, a novel antibody-drug conjugate (ADC) designed for adults with advanced solid tumors. This open-label study focuses on assessing the drug’s safety, tolerability, pharmacokinetics, and early signs of antitumor activity through dose escalation and potential expansion phases. BG-C0979 targets ADAM9, a disintegrin and metalloproteinase enzyme overexpressed in various cancers, delivering a topoisomerase I (TOPO1) inhibitor payload directly to tumor cells to minimize off-target effects and enhance potency.

In prostate cancer, ADAM9 holds particular promise due to its consistent overexpression in malignant tissues compared to benign prostate, where it correlates with aggressive disease and poor prognosis. High ADAM9 expression independently predicts shorter PSA relapse-free survival after radical prostatectomy and is linked to hormone therapy resistance, as seen in the transition from hormone-sensitive to castration-resistant prostate cancer (CRPC). Knocking down ADAM9 in preclinical models suppresses prostate tumor growth, inhibits metastasis to bone, and disrupts cell cycle progression via pathways like REG4, highlighting its functional importance.

Preclinical studies of ADAM9-targeted ADCs, including those similar to BG-C0979, demonstrate sub-nanomolar potency (IC50 0.1-65 pM), bystander killing of nearby cells, and tumor regressions in patient-derived xenograft models across solid tumors. The drug’s design addresses challenges seen in prior ADAM9 ADCs, such as ocular toxicity, while showing good tolerability in non-human primates.

Clinical trial.