768P - Preliminary results of an open-label, multicentric, phase Ib/II study to assess the safety and efficacy of AsiDNA, a DNA repair inhibitor, in addition to PARP inhibitor in patients with relapsed platinum sensitive ovarian cancer already treated with PARPi for at least 6 months (RevoCAN)

Background

The duration of progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer after response to platinum-based therapy is significantly longer with poly (ADP-ribose) polymerase inhibitors (PARPi). Unfortunately, after initial disease control, resistance to PARPi always occurs at some point. AsiDNA™ is a first-in-class DNA damage repair (DDR) inhibitor designed to prevent the repair of DNA damage in tumor cells. It is an oligonucleotide that mimics DNA double strand breaks, producing a false signal noise which acts as a decoy to disrupt the DDR at the “real” sites of DNA damage. The objective was to reverse acquired resistance to PARPi.

Methods

Patients (pts) who received a PARPi (niraparib, olaparib or rucaparib) in maintenance after platinum-based therapy for at least 6 months and who had an isolated increase of CA125 according to Rustin criteria without RECIST progression were includable. Part A: to assess the feasibility of the association of AsiDNA™ 600 mg in a IV weekly perfusion (higher active dose) + PARPi (last dose taken by the patient before entering the study) Part B: to assess the preliminary efficacy on CA-125 (decrease of 50%). Evaluation was to be done at 10, 15, 20 and 25 pts.

Results

6 patients were included in the dose de-escalation part. No DLT was observed (no related gr 3-4 AE). No more gr 3-4 AE was observed during the treatment of the 10 patients. Among the 10 patients evaluable for efficacy, none had a CA125 response. However, according to RECIST criteria, there were 6 pts with a stable disease, 1 with complete response and 3 with progressive disease. Study was stopped after 12 pts (the company stopped the fabrication of AsiDNA™ for new pts).

Conclusions

AsiDNA in addition to PARPi in pts with biological progression under PARPi is safe, and stabilization (> 6 months) has been observed in 3 pts.

Clinical trial identification

EudraCT 2020-000825-18.

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy Cancer campus.

Funding

ONXEO.

Disclosure

P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020 : Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021 : AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Advisory Board, 2022: MSD; Financial Interests, Personal and Institutional, Research Grant: PharmaMar; Financial Interests, Research Grant: ONXEO. F. Bazan: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Novartis, Eisai, Menarini; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape; Financial Interests, Personal, Writing Engagement, Educational: Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AZ, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AZ; Financial Interests, Institutional, Funding, CI clinical trial: AZ; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE Immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AZ; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer; Non-Financial Interests, Member: GCIG. All other authors have declared no conflicts of interest.