Dual targets, singular promise: A comprehensive analysis of bispecific antibodies in solid tumor oncology.

Abstract

e14505 Background: Bispecific Antibodies (BsAbs) represent a novel class of immunoglobulins that can target and bind to two distinct antigens simultaneously. The global BsAb market, valued at approximately USD 8.65 billion in 2023, reflects a tremendous promise and substantial growth. Here, we present a comprehensive analysis of the current BsAbs research pipeline in solid tumors. Methods: Data were extracted from LARVOL CLIN, an outcomes database storing over 100,000 trials, to analyze the number of BsAbs including the number of trials per company, timeline of trials 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, Australian registry ANZCTR and the Asian Registries ChiCTR and UMIN. Results: Our analysis identified 681 registered clinical trials in ClinicalTrials.gov, a number that has doubled since 2020, 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 focus. 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. Amongst oncogene-targeted BsAbs, EGFR is the most prevalent (n=80, 11.7%), followed by HER2 (n=77, 11.3%), and ALK (n=41, 6%). Only 38% of trials specified a biomarker inclusion. HER2-positive alterations (n=35, 5%), followed by PD-L1 expression (n=33, 4.8%) and EGFR mutations (n=26, 3.8%) garnered the most attention. 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 dominate the highest number of trials. Conclusions: Since 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 a key to paving the way for the next era of immune and precision oncology.