Journal Article

TALASUR trial: a single arm phase II trial assessing efficacy and safety of TALazoparib and Avelumab as maintenance therapy in platinum-Sensitive metastatic or locally advanced URothelial carcinoma

Goardon, Nicolas, Bonnet, Isabelle, Boutrois, Jeremy, Brachet, Pierre-Emmanuel, Meriaux, Emeline, Lequesne, Justine, Joly, Florence, Castera, Marie, Coquan, Elodie, Clarisse, Bénédicte, Travers, Romain, Grellard, Jean-Michel, Thiery-Vuillemin, Antoine, Nevière, Zoé

2022

Overview

Background Urothelial carcinoma (UC) is the ninth most commonly diagnosed cancer worldwide, with a 3.8/1 male to female ratio. Platinum-based chemotherapy is the first line standard of care for fit patients with advanced UC. However, despite a response rate (RR) for approximately half of patients receiving standard chemotherapy, durable responses are rare (median progression-free progression (PFS) around 8 months). Recently, immune checkpoint inhibitors (ICI) have emerged as new therapeutic options. Among them, Avelumab, an anti-PD-L1 antibody, was assessed in maintenance treatment, demonstrating an overall survival improvement in the JAVELIN Bladder-100 phase III trial. These findings led to its approval as first line maintenance therapy for patients with locally advanced or metastatic UC who have not progressed on prior platinum-containing chemotherapy. However, disease progression as best response was noticed for 37% of patients under Avelumab as maintenance treatment. UC has targetable genomic alterations, including DNA damage repair (DDR) alterations. DDR deficiency is known to major sensitivity to both platinum-based chemotherapy and PD-1/PD-L1 blockade and the combination of ICI and PARP inhibitors showed promising results. It therefore warrants to assess the interest of combining ICI plus PARP inhibitors as maintenance treatment in UC patients. Methods The TALASUR trial is a single-arm multicenter phase 2 study aiming to assess the antitumor activity of the combination of Avelumab with Talazoparib among patients with locally advanced/metastatic UC in maintenance therapy after platinum-based chemotherapy. The primary objective is to determine the efficacy of the combination, assessed through PFS. Secondary objectives are as follows: safety profile of the association, objective response, duration of tumoral response, disease control rate, time to subsequent therapy, quality of life. A blood and tumor collections will be also constituted. Patient will receive the combination therapy of daily oral Talazoparib (1 mg/day) and intra-venous Avelumab 800 mg on days 1 and 15, in a 28-day cycle. Fifty patients will be enrolled. Discussion Talazoparib with Avelumab combination may have additive activity when administrated jointly. We hypothesize that combination will increase the antitumor activity in UC first line maintenance setting with an acceptable safety profile. Trial registration NCT04678362, registered December 21, 2020. Protocol version: Version 1.3 dated from 2020 09 11.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antitumor activity / Anti–PD-L1 / Biomarkers / Biomedical and Life Sciences / Biomedicine / Bladder / Bladder cancer / Breast cancer / Cancer Research / Cancer therapies / Carcinoma, Transitional Cell - drug therapy / Carcinoma, Transitional Cell - pathology / Chemotherapy / Chemotherapy, Combination / Disease control / DNA damage / DNA repair / Drug therapy / Female / Genotype & phenotype / Health Promotion and Disease Prevention / Humans / Immune checkpoint inhibitors / Immunotherapy / Maintenance treatment / Male / Medical prognosis / Medicine/Public Health / Metastases / Metastasis / Monoclonal antibodies / Mutation / Oncology / Ovarian cancer / PARP inhibitors / Patient outcomes / PD-1 protein / PD-L1 protein / Platinum / Platinum - therapeutic use / Poly(ADP-ribose) polymerase / Poly(ADP-ribose) Polymerase Inhibitors / Prostate / Quality of Life / Safety / Study Protocol / Surgical Oncology / Targeted cancer therapy / Testing / Tumors / Urinary Bladder Neoplasms - drug therapy / Urinary Bladder Neoplasms - pathology / Urothelial carcinoma