Rationale and objectives • Renal cell carcinoma (RCC) accounts for 3-5% of all malignancies, being the sixth most frequently diagnosed cancer in women, and the tenth in men, respectively [1]. Conversely, in the last decades, the treatment landscape of metastatic RCC has been revolutionized by highly effective agents, namely tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICIs) [2]. However, despite the recent remarkable survival improvement achieved by new drugs and combinations, metastatic RCC (mRCC) remains highly lethal, since approximately 134,000 deaths occur, compared with 295,000 new diagnoses per year [3]. • In recent years, a novel class of anticancer drugs characterized by a "smart chemotherapy delivery" has been developed for the treatment of hematological and solid malignancies: the antibody-drug conjugates (ADC) [4]. • ADCs have shown a progressive and steady improvement in terms of therapeutic efficacy and safety leading to the expansion of the therapeutic armamentarium of several types of cancers, However, there is currently no ADC approved for RCC treatment. • Considering the rapid evolution of ADC and their remarkable activity against multiple cancers resulting in approvals in different indications, we decided to evaluate the available evidence on ADC as potential treatment for patients affected by RCC. . Seach strategy • MEDLINE will be systematically searched from inception to June 05, 2023, for eligible studies without any filters, according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines [5]. Inclusion Criteria • All publications focused on preclinical or clinical studies on ADC in RCC patients will be included. The search strategy is to establish through a discussion among all the authors. The following syntax will be used: “(antibody-drug conjugate OR antibody drug conjugate) AND (renal cancer OR kidney cancer OR renal cell carcinoma* OR renal cell cancer)”. Subsequently, PubMed database from its inception to June 05,2023 will be searched. Data selection and extraction • A two-stage study selection process will be use for literature search, and it will be performed independently by two of the authors. Firstly, titles and abstracts were initially screened for potential relevance. Secondly, full texts of relevant results will be retrieved and further assessed for eligibility. A third author will be required to resolve disagreements on study selection by consensus at both stages. Lastly, the two authors agreed on the publications to be included in the scoping review before beginning the data charting process. The following data will be extracted: • Study characteristics: first author name, publication date, journal of publication, study design, number of patients reported. • Study characteristics: phase, primary and secondary outcomes (Overall Survivor and Progression Free Survival according to the response evaluation criteria in solid tumors (RECIST)), efficacy, adverse effects, and tolerability on patients and year of publication. Risk of bias assessment Each individual article will be reviewed by an independent researcher using a scale to assess the validity of the proposed data [6]. In addition, all articles deemed valid for review will be evaluated by 2 independent researchers, and in case of discrepancies, a third author will evaluate the discordant elements. 1. Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2022. CA Cancer J Clin 2022, 72, 7–33, doi:10.3322/caac.21708. 2. Rassy, E.; Flippot, R.; Albiges, L. Tyrosine Kinase Inhibitors and Immunotherapy Combinations in Renal Cell Carcinoma. Ther Adv Med Oncol 2020, 12, 1758835920907504, doi:10.1177/1758835920907504. 3. Klapper, J.A.; Downey, S.G.; Smith, F.O.; Yang, J.C.; Hughes, M.S.; Kammula, U.S.; Sherry, R.M.; Royal, R.E.; Steinberg, S.M.; Rosenberg, S. High-Dose Interleukin-2 for the Treatment of Metastatic Renal Cell Carcinoma : A Retrospective Analysis of Response and Survival in Patients Treated in the Surgery Branch at the National Cancer Institute between 1986 and 2006. Cancer 2008, 113, 293–301, doi:10.1002/cncr.23552. 4. Tarantino, P.; Carmagnani Pestana, R.; Corti, C.; Modi, S.; Bardia, A.; Tolaney, S.M.; Cortes, J.; Soria, J.-C.; Curigliano, G. Antibody-Drug Conjugates: Smart Chemotherapy Delivery across Tumor Histologies. CA Cancer J Clin 2022, 72, 165–182, doi:10.3322/caac.21705. 5. Tricco, A.C.; Lillie, E.; Zarin, W.; O’Brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.J.; Horsley, T.; Weeks, L.; et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med 2018, 169, 467–473, doi:10.7326/M18-0850. 6. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 (updated September 2008).