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Phase 2 Formula-01 Study Evaluates DV Combined With BCG for HER2-High NMIBC - Xingliang Tan

December 3, 2025

Xingliang Tan speaks with Ashish Kamat about the Formula-01 phase 2 study evaluating disitamab vedotin combined with BCG in HER2-high-expressing high-risk non-muscle-invasive bladder cancer. The trial enrolled 78 BCG-naive patients with HER2 IHC scores of 2+ to 3+ who received standard BCG instillation for one year plus eight cycles of DV. Previous research identified HER2 as an independent predictor of BCG failure. Results show a one-year disease-free survival rate of 92.2% in the full analysis set and 95.5% in the per-protocol set, compared to 73% historical controls. The discussion explores micropapillary variant exclusion and plans for phase 3 randomized trial pending two-year results in June 2026.

Biographies:

Xingliang Tan, MD, Physician, Sun Yat-sen University Cancer Center, Guangzhou, China

Ashish Kamat, MD, MBBS, Professor of Urology and Wayne B. Duddleston Professor of Cancer Research, University of Texas, MD Anderson Cancer Center, Houston, TX

Related Content:

ESMO 2025: Efficacy and Safety Results from Formula-01: A Phase II Study of Disitamab Vedotin plus BCG in HER2 High Expression High-risk Non-muscle Invasive Bladder Cancer Patients

HER2 in Bladder Cancer: A Frequent but Complex and Dynamic Biomarker - Daniele Raggi

AUA 2025: Neoadjuvant Therapy with Combined Targeted HER2 and Immunotherapy for T2-T4N0-1M0 Bladder Cancer: A Retrospective Multicenter Study

AUA 2025: Preliminary Efficacy and Safety of Disitamab Vedotin Combined with BCG in the Treatment of High-Risk Non-Muscle Invasive Bladder Cancer with HER2 Expression: A Prospective, Open Label, Single-Center Study
Read the Full Video Transcript

Ashish Kamat: Hello, everybody, and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, urological oncologist in Houston, Texas, and it's a pleasure to welcome Professor Xingliang Tan, who is joining us on behalf of Professor Kai Yao to present the efficacy and safety results from Formula-01, a phase 2 study of disitamab vedotin plus BCG in HER2-high-expressing high-risk non-muscle-invasive bladder cancer. So Dr. Tan, eager to hear what you have to say.

Xingliang Tan: Oh, thank you. It is a great honor and pleasure to be invited by UroToday and communicate with Professor Kamat. My name is Xingliang Tan from the Department of Urology at the Sun Yat-sen University Cancer Center. And on behalf of our department director, Professor Yao Kai, I will share our preliminary results of Formula-01. And we know that BCG intravesical instillation is the standard treatment for intermediate and high-risk non-muscle-invasive bladder cancer, and about 30% of patients experienced tumor recurrence or progression within two to three years. And once BCG failure, radical cystectomy is recommended, and decreased in quality of life.

However, there is still lack of available biomarker to predict the BCG efficiency. So in 2023, our retrospective study, which published in EU Oncology, has found that HER2 was an independent marker to predict BCG failure, and about 40% of high-risk non-muscle-invasive bladder cancer patients have HER2 high expression. So, by the HER2 stratification, we can screen out those with HER2 high expression, and high-risk patients have the highest risk of BCG failure. And the comparing with high-risk HER2 low-expression patients, the two-year BCG failure rate increased dramatically, from 24% to 48%, and even up to 81% in five years. About 20% of the notable NMIBC patients are regarded as the most dangerous subgroup, and is the critical bottleneck, which needs to be widely concerned. However, there is still lack of related clinical trials. So, based on the preclinical data, last year, we conducted a prospective phase 2 trial Formula-01, trying to overcome the highest risk of BCG failure population.

The inclusion criteria include the BCG-naive high-risk NMIBC patients with complete tumor resection, and the HER2 IHC score was 2+ to 3+. All patients will receive one year standard BCG instillation, combining with HER2 targeted ADC drug, DV, for eight cycles. The primary endpoint is two-year DFS rate, and we reported the preliminary efficacy and safety results here. So in total, 78 patients were enrolled and included in the full analysis set, we considered the adequate treatment of patients should receive DV injections, at least five cycles and nine times of BCG instillation. Finally, 68 patients were included for the per-protocol set, as shown in the baseline table. All patients were high-grade tumor, and the 73% were T1 high-grade. 80% of patients were HER2 2+, and the rest of 20% were HER2 3+. At the cutoff, median follow-up time of 12 months, only five patients failed in the full analysis set, including three patients recurrence and the two progression. The survival curve indicated that the one-year DFS rate was 92.2%, was higher, and 22.2%, while in the per-protocol set, only two patient recurrence and the one progression. The one-year DFS rates was higher and could even up to 95.5%.

So comparing with our previous data, the combination therapy increased DFS rates from 73% to 92% in one year after surgery. Although the results are not yet matured, the trend of benefits might clear, especially in HER2 high-expression, high-risk patient, and of course the external validation and the further phase 3 randomized clinical trial should be conducted. So the safety of combination regimens was manageable and the DV injection did not increase the risks of disrupting BCG instillation in patients. And the common DV-related adverse events were mostly grade 1 to 2, and the symptom of majority of patients disappeared when DV stopped it. Overall, severe AE was 12.8% of all the patients, and no AE-related death occurred. So in conclusion, the Formula-01 is the first prospective study showing that DV plus BCG intravesical instillation has promising effect and was well tolerated in the high-risk group of HER2 high expression, high-risk BCG-naive patients. And the one-year DFS rate was 92%, and the primary endpoint of two-year will be available in June, 2026. And the genomic and transcriptomic analysis plan to investigate the molecular mechanisms underlying drug resistance and trying to figure out the ideal population. Thank you.

Ashish Kamat: Great. Thank you so much, Dr. Tan, for presenting this very interesting study. We've always been looking for ways to improve the efficacy of BCG, and of course with the recent studies that have been reported using BCG plus IO, one of the things that came to light was how effective BCG clearly is. And if you look at your preliminary results, again, it's a phase 2 study, so single arm, and you're comparing with historical controls. But even comparing with historical controls and looking at the current BCG response rates, these look very impressive. So, certainly something is going on here. In the HER2-positive patients there has been traditionally a correlation with micropapillary histology. Did you look into your cohort and see if these patients could be classified as having micropapillary disease based on just routine immunohistochemistry?

Xingliang Tan: All the patients, we detected the HER2 expression by our pathology, and both of them were HER2 high expression in 2+ to 3+.

Ashish Kamat: Correct. On histologic analyses, were any of these considered micropapillary?

Xingliang Tan: No. All patients was without the histological variant. And it's the urothelial carcinoma, the UC, the common histology.

Ashish Kamat: So, how do you explain that? Because there is a correlation between HER2 over-expression and micropapillary histology, so did you exclude all patients that had micropapillary disease? Was that an exclusion criteria? You have urothelial carcinoma. And micropapillary disease is a variant of urothelial carcinoma. And, traditionally, micropapillary disease and HER2 expression, they correlate. So did you look at micropapillary histologic subtype within this or did you not look at it?

Xingliang Tan: In fact, we have checked all the pathology. And, all the patients, they were the... You see the common type, UC histology without any micropapillary variant type.

Ashish Kamat: Okay. That's interesting. So micropapillary was excluded from the study essentially. And these were-

Xingliang Tan: Yes, it's excluded.

Ashish Kamat: Okay. That's interesting, because one of the things that we are looking and everybody's looking to do is to see if you can actually find a targeted therapy that would improve the outcomes of patients with micropapillary disease with intravesical therapy and BCG. So it would be interesting to see what the results of this would be in the micropapillary cohort in your next phase. What are your plans now? Are you planning to expand this into a phase 3 study? Are you doing multicenter validation? Where are you taking this next?

Xingliang Tan: Our results was the one-year DFS rates. And we know that, 2025, the ESMO also published two breaking LBA studies and explored the efficiency of immunotherapy combined with BCG in the BCG-naive high-risk patients. And the results over three years, over three years, median follow time. So, in this study, we will follow the results, because our final results is the two-year DFS rates. If the results is good, then we will conduct it, the phase 3 study, further to investigate the combination and comparing with the BCG alone to detect it in the HER2 high expression patients, the benefits.

Ashish Kamat: Okay, great. Well, looking forward to of course, the expanded results and for future directions. Thank you very much for taking the time.

Xingliang Tan: Thank you, Dr. Kamat.