Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 06

1643TiP - First-in-human dose-escalation and expansion study (MITOPE) to evaluate mitochondrial PRX3 inhibition by RSO-021 in patients with mesothelioma and other advanced solid tumors

Date

10 Sep 2022

Session

Poster session 06

Topics

Tumour Site

Mesothelioma

Presenters

Sean Dulloo

Citation

Annals of Oncology (2022) 33 (suppl_7): S743-S749. 10.1016/annonc/annonc1076

Authors

S. Dulloo1, D.A. Fennell2, P.W. Szlosarek3, F. Thistlethwaite4, S. Lord5, N.M. Rahman6, A. Greystoke7, B. Cunniff8, J. Dzialo9, C. Poile10, R. Panchal11, J. Duncan12, P. Graham13, A.S. Bexon14, G. Naumov15, J. Spicer16

Author affiliations

  • 1 Oncology Department, Leicester Royal Infirmary - University Hospitals of Leicester NHS Trust, LE1 5WW - Leicester/GB
  • 2 Oncology, Leicester Royal Infirmary - University Hospitals of Leicester NHS Trust, LE1 5WW - Leicester/GB
  • 3 Medical Oncology Dept., St. Bartholomew's Hospital - Barts Health NHS Trust, EC1A 7BE - London/GB
  • 4 Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 5 Oncology, University of Oxford, OX3 7DQ - Oxford/GB
  • 6 Nuffield Department Of Medicine, University of Oxford, OX3 7DQ - Oxford/GB
  • 7 Medical Oncology Department, The Freeman Hospital (NHS Foundation Trust) Northern Centre for Cancer Care, NE7 7DN - Newcastle-upon-Tyne/GB
  • 8 Pathology And Laboratory Medicine, University of Vermont College of Medicine, 05405 - Burlington/US
  • 9 Mesothelioma Research Programme, University of Leicester - Leicester Cancer Research Centre, LE2 7LX - Leicester/GB
  • 10 Oncology, University of Leicester - Leicester Cancer Research Centre, LE2 7LX - Leicester/GB
  • 11 Respiratory Medicine, Leicester Royal Infirmary - University Hospitals of Leicester NHS Trust, LE1 5WW - Leicester/GB
  • 12 Ceo, RS Oncology LLC, 02142 - Cambridge/US
  • 13 Clinical Development, RS Oncology LLC, 02142 - Cambridge/US
  • 14 Dept. Clinical Development And Clinical Research, Bexon Clinical Consulting LLC, 07043 - Montclair/US
  • 15 Coo, RS Oncology LLC, 02142 - Cambridge/US
  • 16 Comprehensive Cancer Centre, KCL - King's College London, WC2R 2LS - London/GB
More

Abstract 1643TiP

Background

Tumor cells generate elevated levels of reactive oxygen species (ROS) and therefore exhibit increased expression and activity of critical ROS scavenging pathways, including the mitochondrial peroxide scavenging enzyme peroxiredoxin 3 (PRX3). RSO–021 is a novel PRX3 inhibitor that inactivates PRX3 through direct covalent adduction of active site cysteine residues, in turn, inducing oxidative stress to levels incompatible with tumor cell survival. Preclinical studies of RSO-021 show that it selectively inhibits mitochondrial PRX3 in transformed cells and is well-tolerated in animal studies, warranting its clinical phase 1/2 evaluation.

Trial design

This open label, non-randomized, phase 1/2 study (MITOPE) seeks to determine the safety, tolerability, pharmacokinetics, pharmacodynamics and RF2D of RSO-021 after intra-pleural administration in patients with malignant pleural effusion (MPE) secondary to mesothelioma or advanced cancer. The study will also evaluate antitumor activity of RSO-021 in two separate expansion cohorts; (1) in patients with MPE (non-mesothelioma) and (2) in patients with MPE from mesothelioma. Secondary and exploratory objectives include evaluating preliminary anti-tumor activity of RSO-021 across the mesothelioma and non-mesothelioma cohorts, and evaluation of the redox status of malignant tissue and immune cells. Treatment will be delivered weekly via an intrapleural catheter until disease progression or toxicity. An accelerated dose escalation scheme will be used with 1 patient per dose level until the first observation of either a treatment-related adverse event of Grade 2 (or greater) severity or a dose-limiting toxicity is observed. The RP2D will be either the MTD or a dose below it that shows efficacy or PD signals. Once the RP2D has been identified, efficacy of RSO-021 will be evaluated in two expansion cohorts with 1) MPE “other solid tumors”, and 2) MPE from mesothelioma. Up to 42 patients will be enrolled collectively for the two expansion cohorts.

Clinical trial identification

NCT05278975.

Editorial acknowledgement

Legal entity responsible for the study

RS Oncology LLC.

Funding

RS Oncology LLC.

Disclosure

D.A. Fennell: Financial Interests, Personal, Invited Speaker, Writing of a diagnostic manual for mesothelioma: BMS; Financial Interests, Institutional, Invited Speaker, research grant: Aldeyra, Boehringer Ingelheim, Astex Therapeutics; Financial Interests, Personal, Funding, advisory board: Inventiva; Financial Interests, Personal, Invited Speaker, Advisory board: atara; Financial Interests, Institutional, Other, consultant: lab 21; Financial Interests, Institutional, Other, advisory board: Targovax; Non-Financial Interests, Principal Investigator, drug provision for a trial: Clovis Oncology, Eli Lilly, Roche, MSD, Bergen Bio. P.W. Szlosarek: Financial Interests, Personal, Advisory Board, Honorarium: Merck KGaA; Financial Interests, Institutional, Research Grant, Laboratory and clinical trial research funding: Polaris Pharmaceuticals, Inc.; Non-Financial Interests, Advisory Role, Scientific Advisory Board Member: Mesothelioma Applied Research Foundation. F. Thistlethwaite: Financial Interests, Personal, Advisory Board, honoraria: Bayer; Financial Interests, Personal, Advisory Board, Ad board: BMS, Zelluna; Financial Interests, Personal, Advisory Board, Ad boards: GSK; Financial Interests, Personal, Advisory Board, Adboard/consultancy: Tknife; Financial Interests, Personal, Advisory Board: Adicet, Janssen, EnaraBio, Immatics, Ixaka; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Other, iMATCH is a 12 partner consortium funded by not for profit Innovate UK (UK government body) partners include commercial, clinical and academic institutes. I am director and my salary (0.2WTE) is supported through this work as a grant to my institution (The Christie NHS foundation trust - not for profit NHS Hospital) from IUK: iMATCH director; Financial Interests, Institutional, Officer, Clinical lead for this 10 partner consortium of clinical academic and commercial partners. My salary is partly supported (approx. 0.05WTE) through this by a grant paid by Innovate UK (a NFP government body) to my institution (The Christie NHS foundation trust a NFP UK Hospital): SAMPLE; Financial Interests, Institutional, Invited Speaker: Pfizer, GenMab, Synthon, CytomX, Incyte, Janssen, Adaptimmune, Aveo, BMS, GSK, Roche, AbbVie, Immunocore, Achilles ltd, Agalimmune Ltd, Kymab Ltd, Chugai, Millenium Pharmaceuticals/Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Other, Panel member for a funding committee (MRC is a UK government NFP organisation): MRC DPFS panel member. S. Lord: Financial Interests, Personal, Advisory Board: Sanofi, Rejuversen; Financial Interests, Personal, Invited Speaker: Sanofi, Prosigna, Eisai, Roche, Pfizer, Novartis; Financial Interests, Personal, Ownership Interest, Co-founder of company: Mitox Therapeutics; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, Piqur Therapeutics, AstraZeneca, Carrick Therapeutics, Sanofi, Merck KGaA, Synthon, Roche, BioInvent International, RS Oncology; Financial Interests, Institutional, Research Grant: Pathios Therapeutics; Non-Financial Interests, Advisory Role: Carrick Therapeutics. A. Greystoke: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Boehringer Ingelheim, Takeda, Roche, Novartis; Financial Interests, Personal, Invited Speaker: Merck, MSD, Pfizer, Janssen; Financial Interests, Institutional, Invited Speaker: MSD, Pfizer, AstraZeneca, Novartis, Achilles; Non-Financial Interests, Advisory Role: National Institue for Health and Clinical Excellence; Other, Clinical Lead for Cancer (paid position): North East Englad and Yorkshire Genomic Laboratory Hub. B. Cunniff: Other, Personal, Other, Scientific consultant: RS Oncology Llc; Financial Interests, Personal, Stocks/Shares, RS Oncology Llc: RS Oncology Llc; Financial Interests, Institutional, Royalties, RS Oncology Llc: RS Oncology Llc; Non-Financial Interests, Institutional, Research Grant: RS Oncology Llc. J. Duncan: Financial Interests, Personal, Member of the Board of Directors: RS Oncology Llc. P. Graham: Financial Interests, Personal, Full or part-time Employment, Part time consultation work.: Bexon Clinical. A.S. Bexon: Financial Interests, Personal, Other, Paid clinical development consultant: RS Oncology; Financial Interests, Personal, Officer, CEO of clinical development consulting company providing services to the pharmaceutical and biotech industries, cooperative groups, hospitals and other consultancy/CRO companies: Bexon Clinical Consulting; Financial Interests, Personal, Stocks/Shares: Vyriad, Sapience. G. Naumov: Financial Interests, Personal, Ownership Interest: RS Oncology Llc. J. Spicer: Financial Interests, Institutional, Advisory Board: Lilly, AstraZeneca, Boehringer Ingelheim, BMS, Genmab, GSK, RS Oncology, Seattle Genetics, Merck; Financial Interests, Personal, Stocks/Shares, Co-founder: Epsilogen; Financial Interests, Institutional, Invited Speaker: Achilles, Genmab, Roche, Seattle Genetics, Starpharma, Trizell, BergenBio, BMS, IO Biotech, MSD; Non-Financial Interests, Invited Speaker, National strategy board: Experimental Cancer Medicine Centres; Non-Financial Interests, Invited Speaker, Steering Committee: British Thoracic Oncology Group. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.