(UroToday.com) The 2026 American Urologic Association (AUA) Annual Meeting hosted an invasive bladder cancer poster session. Dr. Xingliang Tan presented the updated efficacy and safety results from Formula-01, a phase II trial evaluating disitimab vedotin (DV) + intravesical BCG instillations in patients with HER2 high-expression, high-risk, non-muscle invasive bladder cancer (HR-NMIBC).
Although intravesical BCG remains the standard bladder-sparing treatment for HR-NMIBC, a substantial proportion of patients experience recurrence or progression. Reliable biomarkers to predict BCG response are lacking. Investigators previously demonstrated that HER2 overexpression is an independent adverse predictor of BCG efficacy, with HER2-high tumors—representing approximately 35.7% of all HR-NMIBC cases—associated with 1- and 2-year disease-free survival (DFS) rates of only 73.1% and 53.1%, respectively.1 These findings provided the rationale for evaluating DV, a HER2-targeted antibody-drug conjugate, as a strategy to overcome BCG resistance in this biologically defined subgroup.
Formula-01 (ChiCTR2400080767) is a prospective, single-arm phase II trial that enrolled 78 patients with completely resected HR-NMIBC, defined according to AUA/SUO guidelines. Eligibility required HER2 expression of immunohistochemistry (IHC) 2+ or 3+. Patients received DV at 2 mg/kg every two weeks for eight cycles in combination with standard intravesical BCG administered for one year.
The primary endpoint was 2-year DFS. Secondary endpoints included:
- 1-year DFS
- Progression-free survival
- Safety
The enrolled population was enriched for adverse clinicopathologic features. At diagnosis, 73% of patients had T1 disease, and 27% had Ta tumors. Two-thirds of patients (66.7%) had multifocal disease, 55.2% had tumors >3 cm, and 11.5% had concomitant carcinoma in situ. HER2 expression was IHC 2+ in 80.7% and IHC 3+ in 19.3%.
At a median follow-up of 15 months, only six patients experienced recurrence or progression, and no deaths were reported. In the intention-to-treat population, the 6-month and 1-year DFS rates were 97.37% and 92.2%, respectively. These outcomes compare favorably with the investigators’ previously reported historical experience in HER2-high tumors treated with BCG alone, in which the 1-year DFS rate was 73.1%.
The per-protocol analysis included 68 patients who received ≥5 cycles of DV and >9 BCG instillations. Among these patients, only four treatment failures were observed, further supporting the robustness of the efficacy signal.
Treatment was generally well tolerated. The most common treatment-related adverse events were predominantly grade 1–2 and included:
- Anorexia (53.8%)
- Fatigue (51.3%)
- Alopecia (50.0%)
- Peripheral sensory neuropathy (46.2%)
- Alanine aminotransferase elevation (43.6%)
- Rash (26.9%)
Grade 3–4 treatment-related adverse events were reported in 12.8% of patients.
The investigators concluded that disitamab vedotin plus BCG demonstrated promising antitumor activity and acceptable tolerability in patients with HER2-high HR-NMIBC. By targeting a biomarker-defined subgroup with a known high risk of BCG failure, this combination may reduce recurrence and progression and potentially decrease the need for subsequent radical cystectomy.
These results are particularly noteworthy because they represent one of the first biomarker-driven combination strategies in BCG-naïve high-risk NMIBC. If the favorable early DFS outcomes are maintained with longer follow-up, HER2-directed therapy may emerge as an important precision medicine approach for patients with HER2-overexpressing bladder cancer.
Presented by: Xingliang Tan, MD, Physician, 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 American Urological Association (AUA) 2026 Annual Meeting, Washington, DC, Fri, May 15 – Mon, May 18, 2026.
Reference:- 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.