Abstract 1059P
Background
Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in muscle-invasive bladder cancer. However, 60-75% patients (pts) have residual disease after NAC. The efficacy of immune checkpoint inhibitors (ICI) in metastatic MIBC suggests that a combination of NAC + ICI could increase the rate of pCR. ddMVAC is the most commonly used NAC regimen in Europe. We decided to evaluate the safety and efficacy of ddMVAC + durvalumab (D) +/- tremelimumab (T) in a phase I/II trial.
Methods
NEMIO is an open-label randomized phase I/II trial assessing ddMVAC + D (arm A) +/- T (arm B) in the neoadjuvant setting. Pts received 4 cycles of ddMVAC every 2 weeks (w) + 2 cycles of D 1500 mg +/- T 75 mg every 4 w. Cystectomy was performed 4-8 w after the last dose of ddMVAC. The safety run-in phase was planned to include 6 pts in each arm to evaluate the toxicity. The primary endpoint was the dose limiting toxicity (DLT) defined as the rate of grade ≥ 3 treatment-related adverse events (TRAE) up to 3 months after cystectomy. The phase II cohort was planned to expand each arm to a maximum of 60 pts. The co-primary endpoints of the phase II were G≥3 TRAE and pCR. A Bayesian stopping rule was used to monitor toxicity in real time in both phases. We present here the results of the safety run-in phase.
Results
Twelve pts have been enrolled between Dec 2018 and July 2019 in 6 centers. The median age was 59.5 y with predominant ECOG performance status 0 (n=11/12). 3 pts discontinued the treatment due to chemo related toxicities: 2 pts didn’t receive the last cycle of ddMVAC due to G3 fatigue (1 in each arm) and 1 pt stopped after 2 cycles of ddMVAC and 1 cycle of D+T due to G3 renal insufficiency (RI) in arm B. DLT occurred in 2 pts (1 in each arm): G3 acute RI and G3 thrombopenia. No immune-related adverse events have been reported at time of analysis. The G≥3 TRAE were: hematological (n=4), fatigue (n=2), anal abscess (n=1), RI (n=1). All pts underwent cystectomy. A pCR was observed in 8 pts (4 in each arm) and downstaging to ≤ pT1 in 9 pts.
Conclusions
Based on the first 12 pts included, the safety of ddMVAC + D +/- T is acceptable. The phase II is ongoing and the recruitment is expected to be completed in 2022.
Clinical trial identification
NCT03549715.
Editorial acknowledgement
Legal entity responsible for the study
ARTIC.
Funding
AstraZeneca.
Disclosure
C. Thibault: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca. D. Pouessel: Honoraria (self): Ipsen; Honoraria (self): BMS; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Sanofi; Honoraria (self): Pfizer; Honoraria (self): Merck; Honoraria (self): Astellas; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (institution): Incyte; Honoraria (institution): BMS; Honoraria (institution): MSD; Travel/Accommodation/Expenses: Pfizer. A. Fléchon: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Travel/Accommodation/Expenses: Roche. D. Borchiellini: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Infinity. P. Barthélémy: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen Cilag; Honoraria (self), Advisory/Consultancy: EusaPharma; Honoraria (self), Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: Ipsen. O. Huillard: Honoraria (self), Travel/Accommodation/Expenses: Sanofi; Honoraria (self): BMS; Honoraria (self): AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Ipsen. F. Audenet: Advisory/Consultancy: Sanofi; Advisory/Consultancy: Janssen; Travel/Accommodation/Expenses: Ferring; Travel/Accommodation/Expenses: Ipsen. S. Oudard: Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Sanofi. All other authors have declared no conflicts of interest.