The Landscape of Bispecific Antibodies in Solid Tumor Oncology: Trends, Challenges, and Opportunities.

backgroundBispecific Antibodies (BsAbs) represent a novel class of immunoglobulins that can target and bind to two distinct antigens simultaneously. The global BsAbs market, valued at approximately USD 8.65 billion in 2023, reflects tremendous promise and substantial growth. Here, we present a comprehensive analysis of the current BsAbs research pipeline in solid tumors.

methodsData were extracted from LARVOL CLIN, an outcomes database storing over 130,000 trials, to analyze the number of BsAbs including the number of trials per company, the timeline of trial initiation, phases, specific molecules, targets, and associated biomarkers. LARVOL CLIN leverages regular expression-based text mining to extract data from major trial registries, including ClinicalTrials.gov, EudraCT, the Australian registry ANZCTR and the Asian Registries ChiCTR and UMIN.

resultsOur analysis identified 681 registered clinical trials in ClinicalTrials.gov, a number that has doubled since 2019, each with a known target and phase, evaluating a total of 183 BsAbs. Solid tumors, particularly gastrointestinal, lung, gynecological and breast cancer, have emerged as primary focuses. A significant trend is the strong focus on immune checkpoint bispecific targets, particularly PD1-CTLA4 (n = 216 trials, 31.7%, 4 BsAbs), PD1-VEGF (n = 56 trials, 8.2%, 3 BsAbs), followed by oncogene targets like EGFR-MET (n = 34 trials, 5%, 3 BsAbs). The distribution of clinical molecules also reflects such focus, with dual PD1-CTLA4 inhibitors (Cadonilimab, Volrustomig, Danviostomig) leading the highest number of trials (n = 208, 30.5%). Other promising molecules include Ivonescimab (n = 51, 7.5%), targeting PD1-VEGF, and Amivantamab-vmjw (n = 29, 4.3%), targeting EGFR-MET. Clinical trials investigating PD1-CTLA4 BsAbs showed improved overall survival (OS) and progression-free survival (PFS) with tolerable adverse effects when combined with standard chemotherapy. Only 38% of trials, n = 258, specified a biomarker inclusion. Among oncogene-targeted BsAbs, EGFR is the most prevalent (n = 80, 31%), followed by HER2 (n = 77, 29.8%), and ALK (n = 41, 15.8%). Gene-specific alterations were also represented; HER2-positive alterations garnered the most attention in n = 35 trials. BsAbs development is primarily driven by biotechnology companies (Akesobio, Alphamab, Biokin Pharma, etc.) compared to large pharmaceutical companies (J&J, AstraZeneca, and Boehringer Ingelheim). Geographically, the United States, China and the European Union have the highest number of trials available.

conclusionSince the first BsAb approval in 2014, the field has rapidly expanded, with solid tumor oncology advancing dynamically. The major focus has been on combining BsAbs with immunotherapy strategies, followed by targeting known oncogenic pathways. The shift toward biotechnology-led innovation underscores the growing therapeutic and financial interest in this field. Optimizing the efficacy and safety of these molecules is key to paving the way for the next era of immune and precision oncology.