AsiDNA (etidaligide)

P1/2, N=13, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=26 --> 13 | Trial completion date: Oct 2023 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Apr 2024; Treatment availability issue: The manufacturer of AsiDNA™ decided to cease production to develop an improved version, and the contract ensuring access to this molecule has expired.

P1/2, N=3, Completed, Valerio Therapeutics | Recruiting --> Completed | Phase classification: P1b/2 --> P1/2 | N=115 --> 3 | Trial completion date: Apr 2027 --> Oct 2023 | Trial primary completion date: Dec 2026 --> Oct 2023

Mechanisms comparable to those identified in vitro were detected both in vivo, in the intestine and ex vivo, in precision cut lung slices. Collectively, the results suggest that AsiDNA™ can partially protect healthy tissues from radiation toxicity by triggering a G1/S arrest in normal cells.

P1/2, N=8, Terminated, Institut Curie | Trial completion date: Dec 2023 --> Sep 2023 | Suspended --> Terminated | Trial primary completion date: Dec 2023 --> Sep 2023; IDMC recommendations

P1/2, N=26, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial primary completion date: Oct 2021 --> Oct 2023

P1b/2, N=115, Recruiting, Onxeo | Not yet recruiting --> Recruiting

We used EGFR-mutated (PC9 and HCC827) or ALK-translocated (H3122) lung tumor cells as well as a PC9 xenograft model, to assess whether a long-term combination of AsiDNA and TKI (erlotinib or osimertinib for EGFR-mutated and alectinib for ALK-translocated cells) could prevent the emergence of resistances arising from DTC. Inhibition of the DNA repair machinery using AsiDNA efficiently prevented the emergence of resistances to tyrosine kinase inhibitors and point to the therapeutic opportunity of combining AsiDNA and TKI to overcome resistance in clinical situation. These findings should have immediate implications to design drug combination strategies to prevent TKI-induced resistance in lung cancers.

P1/2, N=26, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris

We used continuous treatment protocols, to select resistance to KRASG12Ci Sotorasib and MRTX849 and assessed the impact of AsiDNA addition on resistance prevention and abrogation. Our results provide the evidence that resistance to KRASG12Ci can evolve from DTC, and point to the therapeutic opportunity of combining AsiDNA and KRASG12Ci to overcome tumor progression or relapse.

Our results suggest that AsiDNA is an attractive candidate to improve radiation therapy in MB, with no indication of additional toxicity in developing brain tissues.

Transcriptome analysis in HDMB03 and DAOY shows an increase in the cellular response with AsiDNA equivalent to a 50% increase of irradiation. Conclusions Our results suggest that AsiDNA is an attractive candidate to improve radiation therapy in pediatric tumors.