The co-expression of antigen targets as a rationale for ADCs combination in urothelial cancer

In a recent issue [ 1 McGregor B.A. Sonpavde G.P. Kwak L. et al. The Double Antibody Drug conjugate (DAD) Phase I trial: Sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. Ann Oncol. 2023; Abstract Full Text Full Text PDF PubMed Google Scholar ], McGregor et al. reported the first clinical trial testing antibody-drug conjugate (ADC) combination in cancers. They treated 24 patients with refractory metastatic urothelial carcinoma (mUC) with the combination of enfortumab-vedotin (EV) and sacituzumab-govitecan (SG). They observed no new safety signal compared to monotherapy and an impressive 70% objective response rate (ORR). The rationale was absence of overlapping major toxicity of ADCs and in vivo synergy of combining SG with microtubule inhibitors. The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinomaAnnals of OncologyVol. 35Issue 1PreviewThe antibody-drug conjugates sacituzumab govitecan (SG) and enfortumab vedotin (EV) are standard monotherapies for metastatic urothelial carcinoma (mUC). Given the different targets and payloads, we evaluated the safety and efficacy of SG + EV in a phase I trial in mUC (NCT04724018). Full-Text PDF