Antibody-drug conjugates (ADCs) have emerged as a promising class of anticancer agents. Currently, the Food and Drug Administration has granted approval to 12 compounds, with 2 later undergoing withdrawal. Moreover, several other compounds are currently under clinical development at different stages. Despite substantial antitumoral activity observed among different tumor types, adverse events and the development of resistance represent significant challenges in their use. Over the last years, an increasing number of clinical trials have been testing these drugs in different combinations with other anticancer agents, such as traditional chemotherapy, immune checkpoint inhibitors, monoclonal antibodies, and small targeted agents, reporting promising results based on possible synergistic effects and a potential for improved treatment outcomes among different tumor types. Here we will review combinations of ADCs with other antitumor agents aiming at describing the current state of the art and future directions.

Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper it provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed.

The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in recent years have fuelled the ongoing development of this class of drugs. These novel agents combine the benefits of high specific targeting of oncogenic cell surface antigens with the additional cell kill from high potency cytotoxic payloads, thus achieving wider therapeutic windows. This review will summarise the clinical activity of ADCs in tumour types not covered elsewhere in this issue, such as gastrointestinal (GI) and genitourinary (GU) cancers and glioblastoma (GBM). In addition to the ongoing clinical testing of existing ADCs, there is substantial preclinical and early phase testing of newer ADCs or ADC incorporating strategies. This review will provide selected insights into such future development, focusing on the development of novel ADCs against new antigen targets in the tumour microenvironment (TME) and combination of ADCs with immuno-oncology (IO) agents.

Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents. These drugs have been extensively studied both in solid and hematologic malignancies, leading to substantial improvement in the therapeutic landscape for several tumors. Despite no ADC have been yet approved for the treatment of gynecological malignancies, some agents have shown promising results and might have the potential to become part of the standard of care. Among them, mirvetuximab soravtansine has shown activity in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent and in combination. Tisotumab vedotin is active in patients with pre-treated cervical cancer, and further investigation is ongoing. The purpose of this review is to summarize the structural and functional characteristics of ADCs and analyze the most recent and promising data regarding the clinical development of ADCs in gynecological malignancies. The available data on the efficacy of the more studied ADCs in ovarian, endometrial, and cervical cancers will be discussed along with toxicities of special interest, the mechanisms of resistance, and future possible drugs combination.

Antibody-drug conjugates (ADCs) have changed the treatment of breast cancer (BC) in more recent years. BC is a heterogenous group of malignancies with a broad range of histopathological characteristics. ADCs represent a class of therapeutics that combines an antigen-specific antibody backbone bound to a potent cytotoxic agent (the payload), via a linker, contributing to an improved therapeutic index. Currently, three ADCs received approval by the US Food and Drug Administration (FDA) and are in routine clinical use in different treatment settings; many more ADCs are in earlier and later stages of development, and their future approval will improve treatment options for patients with advanced but potentially also early-stage BC over time. Just recently, the results of three phase 3 trials (ASCENT, TULIP, and DESTINY-Breast03) evaluating sacituzumab govitecan (SG), trastuzumab duocarmazine, and trastuzumab deruxtecan (T-DXd) in different treatment settings were presented and showed promising results. This overview focuses on the newer ADCs, including T-DXd and SG, their pharmacology, mechanisms of action, and relevant studies. In addition, the latest results from trials investigating some newer ADCs, in further stages of development are presented.

Targeted immunotherapy has arisen over the past decade to the forefront of cancer care. Notably, targeted therapies such as antibody-drug conjugates (ADCs) are becoming more recognized for a novel approach in cancer treatment. The mechanism of action of ADCs incorporates a monoclonal antibody portion directed against the tumor cell antigen and attached to the tumoricidal portion via chemical linkage. The binding of the monoclonal antibody portion allows for tumor cell internalization of the ADC and precise release of the toxic payload within the cancer cell. Multiple myeloma (MM) is an incurable cancer for which belantamab mafodotin was the first-in-class ADC to achieve United States Food and Drug Administration (FDA) approval for treatment of this disease. Clinical trials are currently evaluating other ADCs in the treatment of MM. In this review, a look at the current ADCs being tested in MM clinical trials with a focus on those that are more promising and a potential next-in-line for FDA approval for treatment of MM is discussed.