A phase II trial of the bispecific CD276xCD3 antibody CC-3 in breast cancer patients with molecular relapse

After primary therapy for early breast cancer (BC), routine surveillance is typically limited to clinical assessment and breast imaging, with distant metastasis screening triggered only by symptoms. Circulating cell-free tumor DNA (ctDNA) detection offers a promising method for monitoring treatment response and earlier detection of recurrence in several cancers, including BC. Personalized ctDNA detection in BC is associated with a 50% relapse rate (RR) at 12 months and 100% at four years after initial detection. Of note, a low tumor burden setting, such as molecular relapse (MR)/ctDNA positivity of BC, provides the optimal setting for immunotherapy. CD276 is overexpressed in BC on tumor cells and vasculature, facilitating effector cell infiltration, an essential mechanism for effective therapeutic targeting. We have developed a bispecific CD276xCD3 antibody, CC-3, which has demonstrated preliminary safety in a first-in-human (FIH) basket trial in patients with metastatic BC (NCT05999396).

Based on our previous work, we have designed a multi-center Phase II trial to evaluate the efficacy and safety of CC-3 in BC with MR, defined by ctDNA positivity following primary therapy. In a run-in phase, three dose levels derived from the FIH trial will be evaluated to determine the optimal weekly dosing regimen based on safety. Subsequently, 30 patients will be treated with CC-3 to assess RR at 12 months (primary endpoint). The sample size is based on an estimated RR of≤25% at 12 months. Secondary endpoints include ctDNA clearance, time from ctDNA detection to relapse, safety and quality of life.

Publication History

Article published online:
04 June 2025