Preliminary efficacy and safety of disitamab vedotin (DV) combined with bacillus Calmette-Guérin (BCG) in the treatment of high-risk non-muscle invasive bladder cancer with HER2 expression: A prospective, open label, single-center study.

Abstract

775 Background: Current treatment for high-risk non-muscle invasive bladder cancer (HR-NMIBC) involves Bacillus Calmette-Guérin (BCG) therapy, or radical cystectomy (RC) especially for patients with very-high-risk features. However, 40%-60% HR-NMIBC pts will relapse after BCG treatment. Moreover there are a high incidence of postoperative complications and a negative impact on health-related quality of life after RC. Disitamab Vedotin (DV) is a novel antibody drug conjugate (ADC) that targets the HER2 protein, however its efficacy and safety in HR-NMIBC are limited.We conducted a prospective, open label, single-center study to evaluate the value of RC48 combined with BCG in HR-NMIBC pts. Methods: In this study, two cohorts of BCG-naive pts with very-high-risk features who refused to undergo RC or did not meet the requirements of RC with HER2 expression (IHC 1+/2+/3+) were enrolled (Cohort A:pts were unable to undergo complete tumor resection or have CIS. Cohort B: pts underwent complete tumor resection). All pts will receive eight cycles of intravenous injection of DV (2mg/kg, once every three weeks) and at least one year of BCG intravesical instillation. The Primary endpoints included the 3-month cCR rate in Cohort A and the 6-month EFS rate in Cohort B. The secondary endpoints were to evaluate additional efficacy end points and safety. Results: From Dec 2023 to Aug 2024, twenty eligible pts(16 male;4 female)were enrolled, with 15 pts in Cohort A and 5 pts in Cohort B. 17 of pts had HER2 high expression (2+ or 3+), and 3 of them had HER2 low expression (1+). As a cut-off date (12-Sep-2024), the cCR rate at 3 months and 6 months were both 100% in 11 and 5 pts of Cohort A and the EFS rate at 6 months was also 100% in 3 pts of Cohort B. 65% (13/20) pts experienced treatment-related adverse events (TRAEs). The most common TRAEs included AST/ALT increase 40%(8/20) ,alopecia 45% (9/20), peripheral sensory neuropathy 35% (7/20), anorexia 10% (2/20) and rash 5% (1/20). Grade 3 TRAEs occurred in 10% (2/20) pts with one peripheral sensory neuropathy caused by DV and one hematuria caused by BCG. 60% (12/20) pts had BCG-related AEs including bladder irritation, fever, arthralgia, conjunctivitis and hematuria. Conclusions: This was the first study to evaluate DV in combination with BCG in the treatment for HR-NMIBC. Preliminary results showed the combination had promising efficacy with a manageable safety profile. This may potentially provide a new bladder-sparing therapy for very HR-NMIBC pts with HER2 expression who refused RC or did not meet the requirements of RC. Clinical trial information: NCT06187506 .