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ROLE OF ONCOTHERAD NANO-IMMNOTHERAPY IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER: AN OPEN-LABEL AND SINGLE-ARM PHASE 1/2 STUDY
Current treatment for high-risk non-muscle-invasive bladder cancer (HRNMIBC) involves Bacillus Calmette-Guérin (BCG) therapy, but treatment options are limited for patients with recurrent or BCG-unresponsive disease. The synthetic nanocompound, Biological Response Modifier - Inorganic Phosphate Complex 1, registered as OncoTherad, leads to the distinct stimulation of the immune system mediated by Toll-like Receptors (TLRs) 2 and 4, resulting in an increased activation of the interferon signaling pathway, and represents a promising therapeutic perspective for BCG-unresponsive NMIBC.
In this study, we aimed to evaluate the safety and efficacy of OncoTherad nano-immunotherapy in patients with BCG-unresponsive NMIBC.
We did this open-label, single-center and single-arm phase 1/2 study (Clinical Trial: RBR-6swqd2) in patients with BCG-unresponsive NMIBC. OncoTherad schedule was initiated with weekly intravesical (120 mg/mL) and intramuscular (25 mg/mL) treatment for 6 consecutive weeks, followed by one every other week application for 3 months and, one monthly application until the end of the treatment (24 months). The primary endpoints were pathological complete response (pCR) rate (absence of HRNMIBC or progressive disease) and recurrence-free survival (RFS). Secondary endpoints were duration of response (DOR) and safety. Patient follow-ups were performed with systematic mapping biopsies of the bladder, cystoscopy and ultrasound every 3 months for the first year and every 6 months thereafter for up to 2 years.
Overall, 56 patients were initially enrolled, and 44 patients (30 male, 14 female; 64 years median age) were included in the OncoTherad treatment. In relation to BCG failure, 59.1% of patients were refractory to BCG, 31.8% relapsing and 9.1% intolerant. At 18-months follow-up, pCR rate was 77.3% (95% CI) and RFS of 16.9 months. Among 34 patients with pCR, the median DOR was 13.1 months. No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment. Grade 1/2 treatment-related adverse events (TRAEs) occurred in 61.4% of patients; most frequently reported TRAEs were dysuria (47.7%), pruritus (40.9%), cystitis (38.6%), arthralgia (29.5%), fatigue (25.0%) and rash (27.3%). Grade 3/4 TRAEs occurred in 5 patients (11.4%).
In conclusion, OncoTherad immunotherapy was safe, efficacious and showed promising antitumour activity in patients with BCG-unresponsive NMIBC who declined or were ineligible for radical cystectomy.
Bladder cancer, Immunotherapy, OncoTherad, Nanotechnology
Oncologia - Tumores Urológicos - Não Próstata
WAGNER JOSÉ FÁVARO, IANNY BRUM REIS, JULIANA MATTOSO GONÇALVES, BIANCA RIBEIRO SOUZA SASAKI, ADRIANO ANGELO CINTRA, ATHANASE BILLIS, NELSON DURÁN, JOÃO CARLOS CARDOSO ALONSO