Evolution and future directions of bispecific antibodies in breast cancer: a global clinical trial landscape analysis

Abstract

, Breast cancer remains the most frequently diagnosed malignancy in women worldwide, with over 2.3 million new cases annually [1]. despite the success of endocrine therapies, chemotherapy, and monoclonal antibodies (e.g., trastuzumab, pertuzumab), a significant therapeutic gap persists for advanced, metastatic, and treatment-refractory cases [2]. resistance mechanisms and tumor heterogeneity necessitate the development of next-generation biologics [3]. Bispecific antibodies (BsAbs) offer a transformative approach by simultaneously engaging two different epitopes, thereby redirecting immune effector cells (t/NK cells) to the tumor microenvironment or dual-inhibiting compensatory signaling pathways [4]. here, we present a systematic landscape analysis of global BsAb clinical trials in breast cancer to identify emerging trends and strategic development gaps. data was extracted from trialtrove, a curated clinical trial intelligence platform that combines records from Clinicaltrials.gov, Who iCtrP, and eU Clinical trials register [5,6]. We focused on the period from 2015 to october 14, 2025. the year 2015 was selected as the starting point to mark the “modern era” of bispecific antibody (BsAb) research and development, a booming wave driven by the FdA approval of the first t-cell engager on december 3, 2014 [7]. We queried for drug type: Bispecific Antibody disease: Breast until october 14th, 2025, and found 164 records. We searched interventional clinical trials related to breast cancer and BsAbs, then manually screened records for eligibility. inclusion criteria were: (i) breast cancer as the target disease; (ii) an interventional design evaluating a BsAb either as monotherapy or in combination; (iii) any clinical phase; and (iv) any geographic region. exclusion criteria were observational studies, preclinical studies, duplicate records, and withdrawn records without usable trial information. We excluded 3 observational studies, 15 trials before 2015, and 22 single target investigations, resulting in 124 valid BsAb trials. two reviewers independently verified target combinations, clinical phase, sponsor type, and geographic distribution, with discrepancies resolved by discussion.