Nuria Kotecki, Christiane Jungels, Frederic Hoerner, Jean-Luc Canon, Benoît Colinet, Olivier de Beaumont
Chemotherapy and radiotherapy represent the backbone of treatment for many cancers at different stages of the disease.While these treatments have been highly effective, recurrence rate of these cancers remain high, partially due to drug resistance and DNA repair mechanisms. AsiDNATM, a first-in-class oligonucleotide
mimicking double-stranded DNA breaks acts as a decoy agonist to DNA damage response in tumour cells. AsiDNATM was investigated in a phase I dose escalation part of DRIIV-1 study, as single agent (part A of the study) in patients with advanced solid tumors who failed standard anticancer therapy. The drug demonstrated to have a favorable safety and pharmacokinetic profiles, and a robust target engagement was evidenced in tumour biopsies. Part A established the dose of 600 mg as the optimal dose for part B and further clinical development. Currently, AsiDNATM is investigated in combination with carboplatin with or without paclitaxel (part B of the study) in
patients with advanced solid tumors candidate to carboplatin,with the objective to sensitize tumors to carboplatin. A total of 9 patients were treated in part B as of October 18th, 2020; 3 in part B1 with the doublet combination of AsiDNATM and carboplatin and 6 in parts B2 with the triplet combination of AsiDNATM with carboplatin and paclitaxel. In this article we discuss 4 case reports of patients with advanced solid tumors treated with AsiDNATM in combination with either carboplatin or carboplatin plus paclitaxel, for which the
treatment with AsiDNATM resulted in long stabilization. Interestingly, delivered doses of carboplatin were maintained a long time beforeoccurrence of toxicities resulting in dose reduction. AsiDNATM may play a key role in new combination strategies aiming to treat aggressive and resistant cancers for which the medical needs remain significant.