(UroToday.com) The 2024 European Society of Medical Oncology (ESMO) Annual Congress held in Barcelona, Spain between September 13th and 17th was host to the presentation of Poster 1971. Dr. Pol Servián presented the RUTIVAC-1 Study: a randomized, double-blind, placebo-controlled Phase I trial evaluating the immunomodulatory Effect of RUTI® in individuals with High-Risk Non-Muscle-Invasive Bladder Cancer Treated with Intravesical BCG.
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. Novel combination therapies are needed to improve BCG efficacy.
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.
In RUTIVAC-1, BCG-naïve patients with high-grade non-muscle invasive bladder cancer (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. 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 measured by rates of recurrence and progression, as well as safety, at 3 years of follow-up.
Dr. Servián reported that a total of 40 patients were randomized to placebo or RUTI® (n=20 each arm). The patient disposition is illustrated in the figure below:
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 assessed 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.
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® (Figure below). The RUTI® group exhibited a more balanced, polyfunctional response with increased levels of CD25+ and CD137+ T cells.
These findings highlight the immunological efficacy of RUTI® in inducing a robust and balanced T-cell response, supporting its potential use in combination with intravesical BCG treatment for high-grade NMIBC.
Efficacy
Over a 3-year follow-up period, 15% (3 patients) in each group experienced NMIBC recurrence. However, 2 patients (5%) in the placebo group progressed to MIBC, with a median time to progression of 16.6 months. The median time to recurrence appeared shorter in the placebo group (3.9 months) compared to the RUTI® group (13.1 months). These results indicate that while the recurrence rates were similar between the two groups, the progression to MIBC and the median time to recurrence suggest potential benefits of the RUTI® vaccine in delaying disease progression and recurrence.
The recurrence-free survival in RUTI® group was 89.5% vs. 83.3% in the placebo arm and this was not significant (p=0.636)/ The progression-free survival was 100% vs. 72.2% and this was significantly better in the RUTI® group (p=0.037), similarly the Event-free survival was significant in favor of RUTI® (89.5% vs. 66.7%, p=0.018).
Safety
RUTI® was safe and well tolerated, there were only two grade 1 injection site reactions in the RUTI® group, no other treatment-related adverse events (TRAEs) were recorded.
Dr. Servián 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 (3.9 vs. 13.1 months) and progression to MIBC (5% vs 0%) observed in the RUTI® vaccinated patients
Presented by: Pol Servián, MD, Department of Urology, Hospital Germans Trias i Pujol, Badalona, Spain.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) Luis Carlos Sarmiento Angulo Foundation via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2024 European Society of Medical Oncology (ESMO) Annual Congress held in Barcelona, Spain between September 13th and 17th