1627TiP - ONCOS-102 and pemetrexed/cisplatin in patients with unresectable malignant pleural mesothelioma

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Drug Development
Mesothelioma
Lung and other Thoracic Tumours
Presenter Santiago Ponce Aix
Citation Annals of Oncology (2017) 28 (suppl_5): v568-v572. 10.1093/annonc/mdx389
Authors S. Ponce Aix1, S. Viteri2, J. Bosch-Borrera3, L. Kuryk4, T. Hakonen4, S. Vetrhus5, M. Jäderberg5, L. Paz-Ares1
  • 1Department Of Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 2Medical Oncology, QuirónSalud Dexeus University Hospital, Instituto Oncológico Dr Rosell (IOR, 8028 - Barcelona/ES
  • 3Oncologia Mèdica, Institut Català D’Oncologia (I.C.O), Girona/ES
  • 4R&d, Targovax OY, Helsinki/FI
  • 5R&d, Targovax ASA, NO-0283 - Oslo/NO

Abstract

Background

Mesothelioma is a rare cancer with poor prognosis and limited treatment options, including surgery, radiotherapy and chemo (pemetrexed + cisplatin/carboplatin). Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM-CSF) – expressing oncolytic adenovirus (Ad5/3-D24-GMCSF). In a prior phase I study of 12 patients (pts) with advanced solid tumors, 40% had stable disease (SD) at 3 months, 11/12 pts had infiltration of CD8+ lymphocytes in lesions, and 10/12 had intralesional PD-L1 expression increase. Lesional immune activation was seen in two pts with mesothelioma.

Trial design

A randomized Phase II study (n = 24) with a non-randomized Phase Ib safety lead-in cohort (n = 6). The study will compare ONCOS-102 and chemo with chemo alone (control arm). Eligible pts have histologically confirmed unresectable disease and are not candidates for curative surgery. Pts can be naïve to chemo, or have received and responded to chemo, but relapsed after at least 6 months thus eligible for renewed chemo treatment. Pts must have measurable disease with tumour accessible to intratumoural injections of ONCOS-102 and biopsies. A Data Safety Monitoring Committee will review data when the first 3 and all 6 pts have completed the Day 64 visit (i.e. after 2 cycles of chemo and 4 injections of ONCOS-102). If safety is acceptable, phase II will start with 10 pts in the control arm, and 14 pts in the experimental arm. Primary objective: Safety. Secondary objectives: 1) Tumour specific immunological activation in peripheral blood and biopsies 2) Response Rate 3) Progression Free Survival 4) Overall Survival and 5) Correlation between immune activation and clinical outcome. Treatment: Single cyclophosphamide dose followed by intratumoral injection of ONCOS-102 at 3x1011viral particles (VPs) on days 1, 4, 8, 36, 78 and 120. Pemetrexed (500mg/m2)/cisplatin(75mg/m2) is given on day 22 and every 3 weeks for a maximum of 6 cycles. Imaging at baseline, Day 64 and 148. Tumor biopsies from both injected and non-injected lesions at baseline and Day 36.

Clinical trial identification

Eudra CT: 2015-005143-13 ClinicalTrials.gov. NCT02879669

Legal entity responsible for the study

Targovax OY, Helsinki, Finland

Funding

Targovax OY, Helsinki, Finland

Disclosure

J. Bosch-Borrera: Scientific advice to BMS, Boehringer-Ingelheim, Roche, Pfizer, Lilly, Pierre Fabre. Research grant from Meda Pharma. L. Kuryk, S. Vetrhus, M. Jäderberg: Employee in Targovax and holds shares and stock options in the Company. T. Hakonen: Employee in Targovax and holds share options in Targovax. L. Paz-Ares: Scientific advice to BMS, MSD, Astra-Zeneca, Roche, Pfizer, Novartis, Lilly, Boehringer, Merck All other authors have declared no conflicts of interest.