Abstract 1780TiP
Background
Muscle invasive bladder cancer (MIBC) can be cured by radical cystectomy (RC), but recurrence rates are high and 5-year (yr) survival is ± 50%. We recently found that pre-operative ipilimumab (ipi) plus nivolumab (nivo) resulted in a pathological complete response (pCR) of 46% at RC.
RC however has a high risk of morbidity and even mortality. Chemoradiotherapy (CRT) is a bladder-sparing alternative with cure rates comparable to RC. Given the high pCR to pre-operative checkpoint inhibition (CPI), CRT instead of RC as local treatment may be feasible even in high-risk patients (pts) who receive CPI.
Trial design
INDI-BLADE is a phase 2 trial in which 50 adult pts with cT2-4aN0-2M0 MIBC are treated with three cycles CPI (ipi 3mg/kg (3) – ipi 1mg/kg (1) plus nivo 3 – nivo 3), followed by CRT with mitomycin C plus 5-FU or capecitabine (an oral prodrug for 5-FU) and concurrent RT. Response is evaluated by a CT chest-abdomen, a multiparametric MRI (mpMRI) of the bladder and cystoscopy. The primary endpoint is the bladder-intact event-free survival (EFS). Events are defined as death by any cause, muscle-invasive-, upper urinary tract-, nodal- or distant recurrence, cystectomy, or switch to cisplatin-based chemotherapy. Assuming a tumor stage distribution of 30% cT2N0M0, 40% cT3-4aN0M0 and 30% N+M0, we aim to achieve a 70% EFS at two yr, based on the pCR of 46% in the NABUCCO study. With a sample size of n=50, we expect to reach a median survival of 46.6 months, assuming a median survival of 24 months in the historical control group (81.32% power; 5% significance level). Key secondary endpoints include overall survival, relapse-free survival, and safety. In addition, we will explore the potential of mpMRI-bladder to detect nonresponse, and we will search for potential biomarkers to predict response to treatment.
Clinical trial identification
NCT05200988, Release date: January 21, 2022.
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Bristol Meyer Squibb and KWF (public funding).
Disclosure
B.W.G. van Rhijn: Financial Interests, Personal, Advisory Board: Ferring, QED therapeutics. J. Boormans: Financial Interests, Institutional, Advisory Role: Merck, MSD, Janssen, Bristol Myers Squibb, Astellas, AstraZeneca, Eight Medical, AMBU, Roche; Financial Interests, Institutional, Funding: Janssen, Decipher, Merck. R. Meijer: Financial Interests, Institutional, Advisory Role: Merck, MSD, Janssen, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Janssen, Astellas, Roche. D. Robbrecht: Financial Interests, Other: Merck AG, Pfizer, Bayer, AstraZeneca, Treatmeds. B.B. Suelmann: Financial Interests, Personal and Institutional, Advisory Role: Pfizer, MSD, BMS, Novartis, Ipsen; Financial Interests, Institutional, Research Grant: Pfizer, Astellas, BMS. M.S. van der Heijden: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Pfizer, Seagen; Non-Financial Interests, Institutional, Other, Investigator-initiated trial: 4SC; Non-Financial Interests, Institutional, Other, Steering Committee Member, Local PI + SSC member: Astra Zenenca, BMS; Non-Financial Interests, Institutional, Funding, Investigator-initiated trial: AstraZeneca, BMS, Roche; Non-Financial Interests, Institutional, Principal Investigator, Local PI: GSK, Seagen; Non-Financial Interests, Institutional, Other, Steering committee member, local PI + study co-PI: Janssen. All other authors have declared no conflicts of interest.