Onxeo Announces Enrollment of First Patient in Phase Ib/II Study Revocan
- Revocan is designed to evaluate the abrogation by AsiDNA™ of tumor resistance to a PARP inhibitor in relapsed ovarian cancer
- First results from Revocan are expected early 2021
Paris (France), October 21, 2020 – 7 pm CEST - Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), (“Onxeo” or “the Company”), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage response (DDR), in particular against rare or resistant cancers, today announced a new milestone in the clinical development of AsiDNA™ with the treatment of the first patient in the Revocan1 phase 1b/2 study designed to evaluate the effect of AsiDNA™, Onxeo’s first-in-class DDR inhibitor, on the acquired resistance to PARP inhibitor (PARPi) niraparib for second line maintenance treatment of relapsed ovarian cancer. First results from this study are expected in early 2021.
Globally, primary and acquired drug resistance and the resulting ineffectiveness of drug treatments are responsible for up to 90% of cancer-related deaths2. Acquired resistance to targeted therapies such as PARPi is a major concern in oncology: most, if not all, patients will eventually develop such a resistance3. Moreover, a new challenge has recently emerged for clinicians treating ovarian cancer patients: cross-resistance between PARP inhibitors and platinum, when resistance to PARPi impairs the efficacy of the subsequent chemotherapy4, especially after relapse, which occurs in 70% of these patients5.
“Beyond tolerability outcomes, the Revocan clinical trial aims to provide the proof-of-concept of AsiDNA™’s ability, when added to a PARP inhibitor, to reverse acquired resistance to this otherwise very effective treatment. Revocan has been designed based on successful in-vivo experiments which closely mirrored its clinical protocol. Provided that the clinical study delivers the same positive results, we expect AsiDNA™ to become the first drug to address the critical challenge of acquired drug resistance.” said Olivier de Beaumont, Chief Medical Officer of Onxeo. “This proof-of-concept study would also pave the way for further clinical trials of AsiDNA™ in combination with other targeted therapies, in major indications with high unmet needs. This unique effect of AsiDNA™ on tumor resistance to treatment would address a major concern to oncologists and provide patients with a novel therapeutic option to better control their disease."
The study plans to enroll up to 26 platinum-sensitive patients who have been treated with niraparib as a second-line maintenance therapy for at least six months, and who experience an elevation in CA 125, a well-established biomarker of ovarian cancer resistance to treatment. CA 125 is routinely measured in standard clinical practice and its rise is correlated to an impending disease progression, later confirmed by scan according to RECIST6 criteria.
Led by Patricia Pautier, medical oncologist at Gustave Roussy (Paris, France) and principal investigator, the trial aims to demonstrate that the addition of AsiDNA™ to PARPi niraparib, when CA 125 has started to rise, leads to a significant and durable reduction of this biomarker, corresponding in a delay in the occurrence of tumor resistance. This would in turn results in stopping or slowing disease progression, thereby delaying the next treatment line as well as potentially increasing its efficacy. Progression-free survival and overall survival will also be assessed as longer term efficacy outcomes.
The first patient in Revocan was treated at Gustave Roussy, the study sponsor under a clinical research agreement concluded with Onxeo in early 2020. Two other institutions7 are expected to start recruiting shortly. Additional centers, part of Arcagy Gineco, the French reference network for gynaecological cancers, will also participate into the study.
1 Revocan = REV (Reversion of resistance) – OC (in Ovarian Cancer) – A (with AsiDNA™) – N (and Niraparib)
2 Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist 2019;2:141-160.
3 Klotz, D.M., Wimberger, P. Overcoming PARP inhibitor resistance in ovarian cancer: what are the most promising strategies. Arch Gynecol Obstet (2020)
4 Leary A. and Frenel JS. Communications at ESMO 2020 – Session ID 261: Mini Oral - Gynaecological cancers 1; Presentations ID 813MO & 5012 – Friday 18 September 2020.
5 Ovarian Cancer Research Alliance (OCRA): https://ocrahope.org/patients/about-ovarian-cancer/recurrence/
6 RECIST (Response Evaluation Criteria in Solid Tumours)
7 Western Cancer Institute (Institut de Cancérologie de l’Ouest – Nantes/St Herblain) & University Hospital Center of Lyon (Hospices Civils de Lyon – CHU Lyon Sud)