Intismeran autogene (V940/mRNA-4157) plus bacillus Calmette-Guérin (BCG) versus BCG alone for high-risk non–muscle-invasive bladder cancer: The phase 2 INTerpath-011 study.

Abstract

TPS882 Background: Transurethral resection of a bladder tumor (TURBT) followed by intravesical BCG is the standard of care for patients with treatment-naive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC). However, many patients develop disease recurrence and progression, and novel therapies are needed to improve outcomes. Intismeran autogene (intismeran) is an individualized neoantigen therapy being evaluated for the treatment of several solid tumor types, including muscle-invasive bladder cancer. Intismeran is hypothesized to enhance the antitumor activity of BCG by eliciting endogenous antitumor T cell responses directed at the unique neoantigens of the tumor. INTerpath-011 (NCT06833073) is a randomized, multicohort, open-label, phase 2 study evaluating efficacy and safety of intismeran plus BCG versus BCG alone (cohort A) and intismeran alone (cohort B; exploratory) in participants with HR NMIBC. Methods: Eligible participants are adults with BCG-naive HR NMIBC (high-grade [HG] Ta, T1, and/or carcinoma in situ [CIS]; cohort A) or BCG-naive or BCG-exposed HR NMIBC (CIS with or without papillary tumors [HG Ta or T1]) who are ineligible for or refuse intravesical therapy (cohort B). BCG naive is defined as either not receiving BCG or having received BCG > 2 years before HR NMIBC recurrence. BCG exposed is defined as having not received adequate BCG dosing and HR NMIBC recurrence within 2 years of the last BCG dose. Participants must undergo TURBT ≤12 weeks before enrollment and provide tumor tissue and blood samples for next-generation sequencing and intismeran production and blood for ctDNA testing. In cohort A, approximately 278 participants will be randomly assigned 1:1 to receive 50 mg intravesical BCG (induction: Q1W for 6 weeks; maintenance: Q1W for 3 weeks at weeks 13, 25, 49, and 73) with or without intismeran 1 mg intramuscularly Q3W for 9 doses. In cohort B, approximately 30 participants will receive intismeran 1 mg intramuscularly Q3W for 9 doses. Disease assessment (urine cytology by blinded independent central review [BICR] and cystoscopy) will occur Q12W (and ≥4 weeks after last BCG dose in cohort A) for the first 2 years and Q24W for years 3-5. Computed tomography urography or magnetic resonance urography will occur Q72W for the first 2 years and Q104W for years 3-5. Primary end points are event-free survival (cohort A) and complete response rate (CRR; cohort B) by BICR. Secondary end points include relapse-free survival, disease-specific survival, overall survival, time to cystectomy, and safety (both cohorts). Additional secondary end points include CRR by BICR and duration of response (DOR) in participants with CIS at baseline treated in cohort A, and DOR in cohort B. Enrollment is ongoing. Previously presented at ESMO Congress 2025, FPN: 3135eTiP, Petros Grivas et al. – Reused with permission. Clinical trial information: NCT06833073 .