Strategic Combinations of Antibody–Drug Conjugates from 2023 to 2025: From Dual Therapies to Innovative ADC-Based Regimens

Antibody-drug conjugates (ADCs) are a potent class of targeted cancer therapies that combine the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapeutic agents. By targeting tumor cells with minimal impact on healthy tissues, ADCs achieve a favorable balance between efficacy and systemic toxicity. This therapeutic modality has demonstrated significant clinical success, as evidenced by the FDA approval of 15 ADCs by 2025, with one later withdrawn due to safety concerns, and indications continuing to expand across various cancer types. Beyond monotherapy, there is growing interest in ADC-based combination strategies aimed at enhancing therapeutic outcomes and managing resistance. Several combinations, especially with chemotherapy, immune checkpoint inhibitors, or molecularly targeted agents, have gained regulatory approval or advanced to late-stage clinical trials. While dual-agent regimens have historically dominated the research landscape, multiplet combinations are also gaining traction and represent a promising frontier in oncology. This evolving paradigm highlights the need for a comprehensive understanding of current ADC combination approaches. In this review, we examine recent clinical advances in ADC-based combinations, with a particular focus on regimens that incorporate FDA-approved ADCs. We also discuss the progression from dual-agent approaches to more complex multiplet strategies across a range of tumor types.