Locally advanced or metastatic urothelial
cancer is an aggressive form of
cancer with high recurrence rates and low survival. Nectin-4 is a
cell adhesion molecule commonly expressed in several
tumors, including high expression in urothelial
cancer.
Enfortumab vedotin is an
antibody-drug conjugate composed of an anti-Nectin-4 humanized
monoclonal antibody linked to the microtubule disrupting agent,
monomethyl auristatin E. In this phase I study (NCT03070990), Japanese patients with locally advanced/metastatic urothelial
cancer treated with prior
chemotherapy, or ineligible for
cisplatin, were randomized 1:1 to receive 1.0 mg/kg (Arm A) or 1.25 mg/kg (Arm B)
enfortumab vedotin on Days 1, 8, and 15 of each 28-day cycle. Assessing the pharmacokinetic and safety/tolerability profiles of
enfortumab vedotin were primary objectives; investigator-assessed antitumor activity (RECIST v1.1) was a secondary objective. Seventeen patients (n = 9, Arm A; n = 8, Arm B) received treatment. Pharmacokinetic data suggest a dose-dependent increase in
enfortumab vedotin maximum concentration and area under the concentration-time curve at Day 7.
Enfortumab vedotin was well tolerated across both doses.
Dysgeusia and
alopecia (n = 9 each) were the most common treatment-related adverse events. Regardless of attribution, grade ≥ 3 adverse events occurring in ≥2 patients were
anemia and
hypertension (n = 2 each). One patient achieved a confirmed complete response (Arm A) and five achieved confirmed partial responses (n = 3, Arm A; n = 2, Arm B). Objective response and disease control rates were 35.3% and 76.5%, respectively. In Japanese patients with locally advanced/metastatic urothelial
cancer,
enfortumab vedotin is well tolerated with preliminary antitumor activity and a pharmacokinetic profile consistent with prior reports.