(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Poster Session B: Urothelial Carcinoma. Dr. Oscar Buisan presented Abstract 801: A heterologous prime-boost strategy using RUTI vaccine to improve the BCG response in non–muscle-invasive bladder cancer patients (RUTIVAC-1 trial).
Transurethral resection of bladder tumor (TURBT) and intravesical BCG instillation remains the standard of care treatment for many bladder tumors. Despite receiving standard-of-care therapy, a non-negligible percentage of patients with non-muscle invasive bladder cancer (NMIBC) have disease recurrence or progression to muscle-invasive disease. To enhance treatment outcomes, novel combination therapies are needed to improve BCG efficacy and reduce the risk of progression.
RUTI® consists of cell wall nanofragments of Mycobacterium tuberculosis strain RUTI in a liposomal suspension, this therapeutic vaccine contains a wide mixture of antigens obtained by M. tuberculosis growth under stress conditions. RUTIVAC-1 (NCT03191578) is a randomized, double-blind, placebo-controlled Phase I trial designed to evaluate the use of RUTI® as a heterologous prime-boost strategy in NMIBC patients.
The inclusion criteria required patients to be male or female, aged ≥18 years, who had undergone TURBT and had a histologically confirmed diagnosis of high-risk NMIBC.
BCG-naïve patients with high-grade NMIBC were randomized 1:1 to receive two subcutaneous doses of either placebo or RUTI® (25 μg) before intravesical BCG therapy or in the placebo arm to receive sterile normal saline solution.
Notably, six days after the second vaccination, the standard iBCG induction course and maintenance therapy were initiated. A follow-up visit was conducted between four and eight weeks after the final iBCG dose of the induction course (W16). For vaccine immunogenicity analysis, blood samples were collected at baseline (prior to the first vaccination), at week 2 and week 6 (before the first and last iBCG doses of the induction course, respectively), and at week. Immune response assessment included Activation-induced marker (AIM) analysis and Ex vivo expression of IFN-y, IL-2 and TNF-a using intracellular cytokine staining (ICS). 
The primary endpoint of the trial was to evaluate the immunological changes after RUTI® vaccination, assessed by flow cytometry. The secondary endpoints were the efficacy of RUTI® measured by rates of recurrence and progression, as well as safety.
Dr. Buisan reported that a total of 40 patients were randomized to placebo or RUTI® (n=20 each arm). Baseline characteristics were similar in both groups. Briefly, the median age was 70 years, 90% of the patients were male, high-grade T1 was present in 65%, Ta disease in 32.5%, and 4% had carcinoma in situ (CIS). The rest of the characteristics are detailed in the table below:
The primary endpoint of the study, which was the assessment of the immunological changes after RUTI®, demonstrated that the RUTI® prime-boost strategy induced a vaccine-specific T-cell response. This response was characterized by a sustained increase over time in specific effector CD4 and CD8 T-cells co-expressing several activation markers, as assessed by flow cytometry. In contrast, the placebo group showed a skewed upregulation of CD4+CD25+ T cells, while the RUTI® group displayed a more balanced, polyfunctional response with increased levels of CD25+, CD137+, OX40+, and CD69+ CD4 T cells as shown in the graphic below. 
Moreover, the boosted effect of the RUTI® vaccine in response to BCG instillation was consistently observed in T cells. Differences were noted between pre-vaccination samples and non-stimulated (ex vivo stimulation) samples of patients who received either placebo or RUTI®. The AIM profile of CD4+ CD25+ CD27 T cells (Treg) were boosted from week 6 to 16.
Additionally, the RUTI® group exhibited a more balanced, polyfunctional response with increased levels of CD25+ and CD137+ T cells and cells producing multiple cytokines.
Efficacy
With Kaplan-Meier 5-year follow-up curves, the recurrence-free survival in RUTI® group was 89.5% vs. 72.2% in the placebo arm and was not significant (p=0.193)/ The progression-free survival was 100% vs. 72.2% and this was significantly better in the RUTI® group (p=0.015). Similarly, the Event-free survival was significant in favor of RUTI® (89.5% vs. 50%, p=0.024).
Dr. Buisan concluded his poster presentation with the following key takeaways:
- The heterologous prime-boost strategy with RUTI® vaccination before intravesical BCG treatment in high-risk NMIBC patients is safe, very well tolerated, and significantly impacts immune response.
- The immunological modulation observed with RUTI® vaccination might be associated with the extended disease-free survival and progression free survival observed in the RUTI® vaccinated patients
- These findings suggest that RUTI vaccination prior to intravesical BCG represents a promising therapeutic strategy for improving clinical outcomes in NMIBC management.
Presented by: Oscar Buisan, MD, Staff Urologist at the Urology Department, Institut Català d'Oncologia (ICO) Hospital Germans Trias i Pujol. Cataluña, Spain.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.