Promising Early Results for Disitamab Vedotin and Pembrolizumab Combo in HER2-Positive Urothelial Cancer

A phase 2 study presented at the European Society for Medical Oncology Congress 2024 examined the efficacy and safety of combining disitamab vedotin, an investigational HER2-directed antibody-drug conjugate, with pembrolizumab in treatment-naive patients with HER2-expressing locally advanced or metastatic urothelial carcinoma (la/mUC). HER2 is expressed in around 50% of la/mUC cases, making it a valuable therapeutic target.

In this trial, 20 patients were enrolled and treated with disitamab vedotin every 2 weeks and pembrolizumab every 6 weeks. The primary endpoint was the confirmed overall response rate (ORR), evaluated through a blinded independent central review (BICR). While BICR-ORR will be reported later, preliminary investigator-assessed results were presented.

On the March 4, 2024, data cutoff, 45% of patients remained on treatment. The median age was 75 years, and 35% of participants were cisplatin-ineligible. Results showed promising efficacy, with an investigator-assessed confirmed ORR of 61.1% in all patients and 76.9% in HER2-low patients. Disease control rates were 94.4% in the overall group and 92.3% in HER2-low patients.

The safety profile was manageable, with all patients experiencing treatment-related adverse events, and the most common being fatigue and diarrhea. Ongoing studies will further evaluate disitamab vedotin and disitamab vedotin plus pembrolizumab against platinum-based chemotherapy in advanced urothelial carcinoma.

This data suggests that disitamab vedotin combined with pembrolizumab may offer a potent therapeutic option for patients with HER2-expressing la/mUC, as noted by the study authors: “Disitamab vedotin+pembrolizumab demonstrated encouraging preliminary activity in patients with HER2-expressing la/mUC with a manageable safety profile and supports further evaluation of this regimen.”