bmn-673 has been researched along with Urinary-Bladder-Neoplasms* in 2 studies
1 trial(s) available for bmn-673 and Urinary-Bladder-Neoplasms
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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.
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.. 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.. 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.. NCT04678362, registered December 21, 2020.. Version 1.3 dated from 2020 09 11. Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Female; Humans; Male; Platinum; Poly(ADP-ribose) Polymerase Inhibitors; Quality of Life; Urinary Bladder Neoplasms | 2022 |
1 other study(ies) available for bmn-673 and Urinary-Bladder-Neoplasms
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Somatic mutation of the cohesin complex subunit confers therapeutic vulnerabilities in cancer.
A synthetic lethality-based strategy has been developed to identify therapeutic targets in cancer harboring tumor-suppressor gene mutations, as exemplified by the effectiveness of poly ADP-ribose polymerase (PARP) inhibitors in BRCA1/2-mutated tumors. However, many synthetic lethal interactors are less reliable due to the fact that such genes usually do not perform fundamental or indispensable functions in the cell. Here, we developed an approach to identifying the "essential lethality" arising from these mutated/deleted essential genes, which are largely tolerated in cancer cells due to genetic redundancy. We uncovered the cohesion subunit SA1 as a putative synthetic-essential target in cancers carrying inactivating mutations of its paralog, SA2. In SA2-deficient Ewing sarcoma and bladder cancer, further depletion of SA1 profoundly and specifically suppressed cancer cell proliferation, survival, and tumorigenic potential. Mechanistically, inhibition of SA1 in the SA2-mutated cells led to premature chromatid separation, dramatic extension of mitotic duration, and consequently, lethal failure of cell division. More importantly, depletion of SA1 rendered those SA2-mutated cells more susceptible to DNA damage, especially double-strand breaks (DSBs), due to reduced functionality of DNA repair. Furthermore, inhibition of SA1 sensitized the SA2-deficient cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with SA2-deficient tumors. Topics: Animals; Antigens, Nuclear; Cell Cycle Proteins; Cell Line, Tumor; Chromosomal Proteins, Non-Histone; Cohesins; DNA Breaks, Double-Stranded; Female; Gene Knockdown Techniques; Genes, Essential; Humans; Mice; Mice, Nude; Mutation; Neoplasms; Nuclear Proteins; Phthalazines; Poly(ADP-ribose) Polymerase Inhibitors; Protein Subunits; Sarcoma, Ewing; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays | 2018 |