Episode 9: Double ADC treatment as a promising approach in mUC: a dose-response trial

In this episode of WND, Prof Emmanuel Seront from UCL Louvain and Prof Vulsteke from Maria Middelares Gent discuss the innovative approach of combining two antibody-drug conjugates in the treatment of metastatic urothelial carcinoma (mUC).

The widely recognized enfortumab vedotin (EV), which targets nectin-4, was paired with sacituzumab govitecan (SG), targeting Trop-2. This approach aims to address two distinct targets with separate payloads and non-overlapping toxicities.

The trial focused on assessing the safety and efficacy of escalating doses of combined SG+EV involving mUC patients who had progressed after chemotherapy. Out of the 24 patients enrolled, there was a 70% ORR, with 3 patients having a complete response and only 3 patients experiencing disease progression.

Toxicity remains a significant concern, particularly with grade 3 adverse events including fatigue, anaemia, and neutrophil depletion. The optimal dose identified in this trial was 8mg/kg of SG and 1.25 mg/kg of EV.

These encouraging trial results open new avenues for the treatment of various malignancies that employ ADC. Further long-term follow-up is required for conclusive assessments, especially in heavily pretreated patients. Additionally, there is potential for exploring additional options, such as combining ADC with checkpoint inhibitors.

Experts concur that the double ADC combination could prove beneficial in the perioperative setting, given that EV monotherapy achieves a response rate of 40%, which nearly doubles to 70% in this combination therapy. Therefore, this groundbreaking trial of combined ADC warrants further investigation and follow-up, particularly for cases requiring a drastic response.