Abstract 3369
Background
Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in non-metastatic muscle-invasive bladder cancer (MIBC). However, 60-75% patients have residual tumor after neoadjuvant cisplatin-gemcitabin or ddMVAC regimen. Pathological complete response (pCR) after NAC is correlated with overall survival (OS). Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe in urothelial carcinoma (UC) in fit patients. The emergence of immune checkpoint inhibitor (ICI) in the metastatic setting raises the question if the combination chemo plus ICI could increase the pCR rate.
Trial design
NEMIO is a French open-label randomized phase II trial assessing in the neoadjuvant setting the combination ddMVAC plus durvalumab (D) alone or in combination with tremelimumab (T): 4 cycles of ddMVAC every 2 weeks + 2 cycles of D (1500 mg) +/- T (75 mg) every 4 weeks. Cystectomy is performed 4-8 weeks after the last dose of ddMVAC. As no safety data are available on the ICI plus ddMVAC combination, 6 pts will be included in each arm in a safety run-in cohort to evaluate the toxicity rate of the 2 regimens. Each arm will be expanded to a maximum of 60 pts according to a Bayesian stopping rule based on grade 3/4 treatment-related adverse events (G 3/4 TRAE). The primary endpoint of the safety run-in phase will be the rate of G3/4 TRAE. The primary endpoint of the phase II will be the pCR rate and G3/4 TRAE. We hypothesized that pCR after ddMVAC + D +/- T will be > or = 45%. Exploratory endpoints will include biomarkers of response and resistance to the combo. Molecular analysis will be conducted on tumor, blood (ctDNA) and urine samples (uDNA). Immunological and metabolomics profile will also be analyzed. Seven patients have yet been enrolled since December 2018 from the 10 French participating centers and we expect the recruitment to be completed in 2021.
Clinical trial identification
NCT03549715.
Editorial acknowledgement
Legal entity responsible for the study
Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie (ARTIC).
Funding
AstraZeneca.
Disclosure
C. Thibault: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. D. Borchiellini: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen. O. Huillard: Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Janssen. P. Barthelemy: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: MSD; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi. D. Pouessel: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte. A. Flechon: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD. H. Blons: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer; Advisory / Consultancy: MSD. S. Oudard: Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Roche. All other authors have declared no conflicts of interest.
Resources from the same session
4614 - Predictors of Response to Checkpoint Inhibitors in Naïve and Ipilimumab-Refractory Melanoma
Presenter: Domenico Mallardo
Session: Poster Display session 3
Resources:
Abstract
2901 - IFN-γ/IL-10 ratio as predictive biomarker for response to anti-PD-1 therapy in metastatic melanoma patients
Presenter: Emilio Giunta
Session: Poster Display session 3
Resources:
Abstract
2306 - Multiplex Chromogenic Immunohistochemistry (IHC) for Spatial Analysis of Checkpoint-Positive Tumor Infiltrating Lymphocytes (TILs)
Presenter: Scott Ely
Session: Poster Display session 3
Resources:
Abstract
1678 - The role of PD-L1 expression as a predictive biomarker in advanced renal cell carcinoma: a meta-analysis of randomized clinical trials.
Presenter: Alberto Carretero-Gonzalez
Session: Poster Display session 3
Resources:
Abstract
5138 - Radiomic Features as a Non-invasive Biomarker to Predict Response to Immunotherapy in Recurrent or Metastatic Urothelial Carcinoma
Presenter: Kye Jin Park
Session: Poster Display session 3
Resources:
Abstract
5800 - Integrative combination of high-plex digital profiling techniques and cluster analysis to reveal complex immune biology in the tumor microenvironment of mesothelioma
Presenter: Carmen Ballesteros-Merino
Session: Poster Display session 3
Resources:
Abstract
5736 - Predictive factors of response to immunotherapy in 198 patients with metastatic non-microcytic lung cancer (mNSCLC): real world data from 2 university hospitals in Spain
Presenter: Juan Felipe Cordoba Ortega
Session: Poster Display session 3
Resources:
Abstract
5645 - Evaluating Lung CT Density Changes Among Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Treated with Thoracic Radiotherapy (TRT) alone or TRT Followed by Combined Ipilimumab (IPI) and Nivolumab (NIVO).
Presenter: Kujtim Latifi
Session: Poster Display session 3
Resources:
Abstract
1540 - Immuno-oncology therapy biomarkers differences between polyoma-virus positive and negative Merkel cell carcinomas
Presenter: Zoran Gatalica
Session: Poster Display session 3
Resources:
Abstract
4538 - Can we improve patient selection for phase 1 clinical trials (Ph1) based on Immuno-Oncology score prognostic index (VIO)?
Presenter: Ignacio Matos Garcia
Session: Poster Display session 3
Resources:
Abstract