The emergence of Nectin-4 as a therapeutic target has opened new possibilities for treating advanced solid tumors. A novel antibody-drug conjugate (ADC), IPH4502, is currently being evaluated in a first-in-human Phase 1 trial. This study is investigating the safety, tolerability, and preliminary efficacy of IPH4502 in patients with advanced solid tumors known to express Nectin-4. Early results have generated considerable interest within the oncology community.

IPH4502 is an ADC that links a Nectin-4-targeting antibody to a potent topoisomerase I inhibitor, exatecan. Preclinical research has shown that this approach delivers highly targeted tumor cell destruction while sparing healthy tissue. This therapeutic strategy holds promise not only for urothelial carcinoma but also for a range of other cancers including breast, lung, ovarian, and pancreatic tumors. By focusing on Nectin-4—a cell surface protein highly expressed in certain cancers—IPH4502 aims to offer a more tailored and effective treatment option.

The Phase 1 study is divided into two parts. The first stage involves a dose-escalation phase guided by a Bayesian optimal interval design with backfilling (BOIN-BF) to determine safe and effective dosing levels. In the second stage, the trial will concentrate on dose optimization within specific indications. Initial data from the trial will help establish the recommended Phase 2 dose (RP2D) and guide further development.

In addition to urothelial carcinoma and other solid tumors, Nectin-4 expression has been observed in prostate cancer. Research published in The Prostate journal examined the potential of Nectin-4-targeted therapies, including enfortumab vedotin, in prostate cancer cell lines. The study found variable Nectin-4 expression across these lines, which could influence treatment outcomes. This highlights the importance of thorough biomarker assessment as the field moves toward more personalized oncology treatments.

Clinical trial.