An antibody–drug conjugate shows promising signs of efficacy in advanced cervical cancer  

The emergence of antibody–drug conjugates

In patients with recurrent or metastatic cervical cancer, treatment options remain limited and are mainly based on chemotherapy, immunotherapy, and anti-angiogenic agents. In recent years, however, a highly promising new class of therapies has emerged in oncology: antibody–drug conjugates.

These innovative treatments act like a “guided missile”: a chemotherapy molecule is linked to an antibody, which is designed to specifically recognise and bind to a protein expressed on 

the surface of cancer cells. While the mechanism of action is not yet fully understood, one of the most likely explanations is the release of chemotherapy inside tumour cells once the complex has bound to and been internalised. This targeted delivery increases treatment efficacy where it is needed while limiting its impact on surrounding healthy cells, thereby reducing the side effects often associated with conventional chemotherapy.

► Watch Professor Loriot’s video explanation

An antibody–drug conjugate targeting the NECTIN-4 protein

During an oral session at the ASCO congress, Professor Yohann Loriot presented the results of an international phase I/II study evaluating the ADC CRB-701, developed by Corbus Pharmaceuticals and previously shown to have promising clinical activity in head and neck cancers. This ADC targets the NECTIN-4 protein, which is expressed on the surface of many solid tumours, including 80% to 90% of cervical cancers.

A total of 72 women with advanced or recurrent cervical cancer were enrolled in the study, which aimed to identify the optimal dose of CRB-701 and evaluate its efficacy. The initial results are encouraging: at a dose of 2.7 mg/kg, more than one in five patients (22.2%) responded to treatment, administered as monotherapy. At a higher dose of 3.6 mg/kg, more than one in three patients (37.5%) benefited. In addition, complete responses were observed in several patients, meaning that all cancer lesions visible on imaging disappeared.

These findings indicate notable efficacy, particularly given that the population had been heavily pretreated. The most common side effects were mainly ocular and general (hair loss and fatigue). This work has also helped to better understand the biological mechanisms underlying the development of keratitis in some patients.

“These encouraging results suggest that CRB-701, a next-generation antibody–drug conjugate targeting the NECTIN-4 protein, could represent a promising therapeutic option for patients with recurrent or metastatic cervical cancer—a disease that still has too few treatment advances worldwide. However, these findings are preliminary, and phase III studies will be essential to confirm these results on a larger scale,” concludes Professor Yohann Loriot.

Abstract n°5508