xevinapant (Debio 1143)

Furthermore, combination treatment significantly downregulated gene expression associated with immune-related pathways, increased levels of immunodysregulatory acute phase proteins and decreased levels of necroptosis mediator RIPK3. Overall, xevinapant plus CRT has an immunosuppressive effect on the tumour-immune microenvironment which may explain its lack of clinical benefit.

NCT03270176 (https://clinicaltrials.gov/study/NCT03270176). Registered on ClinicalTrials.gov on 29 August 2017.

P3, N=19, Terminated, Groupe Oncologie Radiotherapie Tete et Cou | Trial completion date: Mar 2025 --> Sep 2024 | Completed --> Terminated; toxicity

P3, N=19, Completed, Groupe Oncologie Radiotherapie Tete et Cou | Suspended --> Completed | Trial completion date: Oct 2035 --> Mar 2025 | Trial primary completion date: Oct 2025 --> Dec 2024

P3, N=19, Suspended, Groupe Oncologie Radiotherapie Tete et Cou | Trial completion date: Sep 2030 --> Oct 2035 | Trial primary completion date: Oct 2024 --> Oct 2025

P1, N=0, Withdrawn, H. Lee Moffitt Cancer Center and Research Institute | N=12 --> 0 | Recruiting --> Withdrawn

This study demonstrates the therapeutic potential of venetoclax in combination with ATO in vitro and strongly encourages further investigation of relapsed/refractory APL with high BCL2 expression.

P3, N=730, Terminated, EMD Serono Research & Development Institute, Inc. | Trial completion date: Apr 2027 --> Sep 2024 | Active, not recruiting --> Terminated; Study has crossed the pre-defined futility boundary at the Interim Analysis.

P3, N=166, Terminated, EMD Serono Research & Development Institute, Inc. | Active, not recruiting --> Terminated; No major safety concerns were identified in XRAY VISION study, but Lack of evidence of efficacy of meaningful clinical benefit.

P3, N=19, Suspended, Groupe Oncologie Radiotherapie Tete et Cou | Trial primary completion date: Jul 2024 --> Oct 2024

P1, N=18, Terminated, EMD Serono Research & Development Institute, Inc. | Active, not recruiting --> Terminated; No major safety concerns were identified in HyperlynX study, but Lack of evidence of efficacy of meaningful clinical benefit.

Several Survivin inhibitors, including YM-155, Debio1143, EM1421, LQZ-7I, and TL32711, have emerged as potential anticancer drugs awaiting validation in clinical trials. Furthermore, Wi-AREAL treatment activated apoptosis signaling, as evidenced by reduced PARP-1 and Bcl-2 levels, increased procaspase-3, and elevated Cytochrome C. Additionally, treating cells with a nontoxic low concentration (0.01%) of Wi-AREAL inhibited migration and invasion, as well as EMT (epithelial-mesenchymal transition) signaling. By combining computational and experimental approaches, we demonstrate the potential of Wi-A and Wi-AREAL as natural inhibitors of Survivin, which may be helpful in cancer treatment.