Dr Chauhan on DLL3 Expression and Obrixtamig Outcomes in DAREON-7

Aman Chauhan, MD, breaks down how DLL3 expression level affected both safety and efficacy in the phase 1 DAREON-7 study of obrixtamig (BI 764532) plus chemotherapy, data he presented at the 2026 North American Neuroendocrine Tumor Society (NANETS) Symposium.

Chauhan, associate professor of medicine at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, explains that DLL3 positivity was an entry criterion for DAREON-7, with patients required to have expression of 1% or higher. Roughly 80% of the patient population screened had DLL3 expression, which Chauhan describes as encouraging confirmation that the target is present in most patients with this disease. Within that group, the split between high and low expressers was close to even. About 55% had DLL3 expression above 50%, and about 45% fell below that threshold, which set up the central question of whether expression level changes what patients experience.

On safety, Chauhan reports no concerning signals of toxicity associated with high DLL3 expression, a finding he calls very reassuring in the context of a phase 1 trial. The adverse event profile was very similar between the two groups. To his pleasant surprise, no grade 3 or grade 4 cytokine release syndrome events occurred in either the high or the low cohort. He attributes that result in part to the combination effect of the chemotherapy. Chauhan notes that grade 3 and 4 cytokine release syndrome rates were already in the single digits with single-agent obrixtamig, which makes a rate of zero in this study notable.

Turning to efficacy, Chauhan reports that agnostic of DLL3 expression level, the vast majority of patients responded, with a 77% response rate he characterizes as a dream come true for any drug developer and trialist. Dissected by expression, the response rate in the DLL3-high group was approximately 87%.

Chauhan notes that it could be suggested that responses might be attributable to chemotherapy rather than obrixtamig; however, he points to durability as the answer. Responses lasted almost a year, which he says is not seen with chemotherapy based on extensive historical data, leading him to conclude the deep and durable responses were driven by obrixtamig.

A subgroup analysis of landmark progression-free survival added further context. Almost one-third of patients were either stable or responding at the 1-year mark, and in the DLL3-high population that figure approached 50%. Chauhan frames the significance against a disease in which median survival was a year, noting that a large share of patients on first-line therapy alone were alive at one year.