(UroToday.com) The 2025 European Society for Medical Oncology (ESMO) Annual Congress held in Berlin, Germany was host to a urothelial carcinoma poster session. Dr. Xingliang Tan presented the efficacy and safety results from Formula-01, a phase II study of disitimab vedotin + BCG in high-risk, non-muscle invasive bladder cancer (NMIBC) patients with a high HER2 expression.
Dr. Tan highlighted that there are currently no validated biomarkers to predict BCG response in high-risk NMIBC patients. Dr. Tan and his group were the first to demonstrate that high HER2 expression was an independent predictor of an unfavorable response to intravesical BCG therapy, with high-risk NIMBC patients having high HER2 expression (~36% of all high-risk NMIBC) more likely to experience BCG failure (1- and 2-year disease-free survival [DFS] rates: 73% and 53%, respectively).1 Disitamab Vedotin (DV) is a novel anti-HER2 antibody-drug conjugate that is hypothesized to improve outcomes in HER2 high expression high-risk NMIBC patients. The study objective was to evaluate the efficacy and safety of DV + BCG in HER2 high-expression high-risk NMIBC.
Formula-01 (ChiCTR2400080767) is a prospective, phase II trial that enrolled 78 patients meeting the following eligibility criteria:
- Underwent complete TURBT
- High-risk NMIBC based on the AUA/SUO guidelines
- Pure urothelial carcinoma
- HER2 expression: IHC 2/3+
- BCG-naïve
Eligible patients received DV (2 mg/kg every 2 weeks x 8 cycles) and BCG instillation for one year. The primary endpoint was the 2-year DFS rate, and the secondary endpoints were 1-year DFS rate, progression-free survival (PFS), and tolerability. Herein, Dr. Tan presented the preliminary efficacy and safety results.
Overall, 82 patients were screened, and 78 were enrolled and received treatment. 68/78 patients completed the 1-year treatment, with 10 patients discontinuing therapy for the following reasons:
- Withdrew consent: 2
- Incomplete BCG induction instillation: 5
- Incomplete DV treatment (<5 cycles): 3
The baseline patient characteristics are summarized below. The median patient age was 64 years. HER2 IHC expression was 2+ and 3+ in 81% and 19%, respectively. 73% had cT1 disease. 12% of patients had concomitant CIS. 55% of patients each had multifocal disease and tumors ≥3 cm. 49% of patients underwent a re-staging TURBT. 15% of patients had AUA very high-risk disease, with the remaining 85% AUA high-risk.
At a median follow-up of 12.1 months, 5 patients (6.4%) experienced disease recurrence or progression and no deaths were observed. In the per-protocol set (n=68; received DV ≥ 5 cycles and BCG > 9 cycles), only two patients (3%) experienced treatment failure. Overall, the 6- and 12-months DFS rates in the intent-to-treat population were 97% and 92%, respectively. Common DV-related adverse events were mostly Grade 1-2 in nature and included:
- Anorexia (54%)
- Fatigue (51%)
- Alopecia (50%)
- Peripheral sensory neuropathy (46%)
- ALT elevation (44%)
- Rash (27%)
Grade 3-4 treatment-related adverse events were reported in 13% of patients.
Dr. Tan concluded as follows:
- Formula-01 is the first prospective study to demonstrate that the combination of disitamab vedotin + BCG is associated with excellent efficacy outcomes in high-risk NMIBC patients with high HER2 expression.
- 12 months DFS rate: 92%
- Disitamab vedotin did not delay BCG instillation, and the safety profile was manageable.
Presented by: Xingliang Tan, MD, Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center – Tucson, AZ, @rksayyid on X during the 2025 European Society for Medical Oncology (ESMO) Annual Congress, Berlin, Germany, October 17–21, 2025
Related content: Phase 2 Formula-01 Study Evaluates DV Combined With BCG for HER2-High NMIBC - Xingliang Tan
References:
- Tan X ,Liu Z, Cai T, et al. Prognostic Significance of HER2 Expression in Patients with Bacillus Calmette-Guérin-exposed Non-muscle-invasive Bladder Cancer. Eur Urol Oncol. 2024; 7(4):760-9.