BeOne Medicines launches ADAM9-targeted ADC into first-in-human study

BeOne Medicines, the global oncology company formerly known as BeiGene, has registered a clinical trial for BG-C0979, the first ADAM9-targeted antibody-drug conjugate (ADC) carrying a topoisomerase I (TOP1) payload to enter clinical development. The Phase Ia/b study (NCT07414836), posted on ClinicalTrials.gov in February 2026, plans to enroll 84 adults with advanced, metastatic, or unresectable solid tumors. Dosing is expected to begin by Q2 2026, with primary completion projected for Q2 2029. The trial is open-label, non-randomized, and sequential in design, and will evaluate BG-C0979 both as monotherapy and in combination with Tevimbra (tislelizumab; BGB-A317), the company’s marketed anti-PD-1 checkpoint inhibitor.

The research rationale

ADAM9, or A Disintegrin and Metalloproteinase 9, is a transmembrane protein involved in ectodomain shedding of growth factors, integrin-mediated cell adhesion, and extracellular matrix remodeling — processes that collectively facilitate tumor invasion and metastatic spread. Preclinical literature has documented ADAM9 overexpression across a range of solid malignancies, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, triple-negative breast cancer, gastric cancer, and castration-resistant prostate cancer, while expression in normal adult tissues remains comparatively low.

The BG-C0979 ADC Phase I study is not the first clinical program to pursue ADAM9. MacroGenics and ImmunoGen (now part of AbbVie) advanced IMGC936, an ADAM9 ADC, into a Phase I/II trial (NCT05392973) in advanced solid tumors in 2023. Development of that molecule has been discontinued.

BG-C0979 is differentiated by its payload class. The trial’s exclusion criteria bar patients who have received prior ADAM9-targeted ADCs or ADCs containing a TOPO1 inhibitor, confirming that BG-C0979 carries a camptothecin-derived warhead — the same payload class that underpins trastuzumab deruxtecan (Enhertu) and sacituzumab govitecan (Trodelvy), two of the most commercially and clinically consequential ADCs of the past five years. Coupling that payload to an ADAM9-binding antibody could, in principle, extend TOPO1-mediated cytotoxicity to tumor types that lack the established ADC targets (HER2, TROP2) at sufficient density for existing agents.

One detail embedded in the protocol deserves attention: the inclusion of castration-resistant prostate cancer-specific endpoints. Prostate-specific antigen (PSA) response, defined as a 50% or greater decline from baseline confirmed at least three weeks later, and radiographic progression-free survival assessed by PCWG3 criteria for bone lesions, are both listed as secondary measures. This signals that CRPC is a tumor type of particular interest to the sponsor, even though the trial’s eligibility criteria are written broadly enough to accommodate a basket of ADAM9-expressing malignancies.

The broader landscape for antibody-drug conjugates in solid tumors is intensely competitive. Trastuzumab deruxtecan (Daiichi Sankyo/AstraZeneca), sacituzumab govitecan (Gilead), datopotamab deruxtecan (Daiichi Sankyo/AstraZeneca), and enfortumab vedotin (Astellas/Pfizer) are all approved and expanding into additional indications. Dozens more ADCs targeting HER2, TROP2, HER3, B7-H3, Nectin-4, Claudin 18.2, c-MET, and other antigens are in Phase II or Phase III development. Against that backdrop, ADAM9 remains a comparatively uncrowded target.

For BG-C0979, the competitive question is less about ADAM9-on-ADAM9 rivalry and more about whether this target can carve out clinical utility in patient populations already served — or soon to be served — by ADCs against other antigens, by KRAS inhibitors (sotorasib, adagrasib, divarasib), by bispecific antibodies (tarlatamab, ivonescimab, amivantamab), or by radioligand therapies such as lutetium-177-PSMA-617 (Pluvicto) in CRPC. The inclusion of a tislelizumab combination arm reflects an increasingly standard hypothesis in the ADC field: that TOPO1-payload ADCs can induce immunogenic cell death, priming tumors for enhanced responses to PD-1 blockade.