Abstract 819TiP
Background
Cervical cancer is the fourth most frequent cancer in women with a survival rate <20% for advanced stages. It mainly results from chronic infection with human papillomavirus. Standard first-line therapy is RTCT for cervical cancer FIGO stage IB3 and more. Recent evidence in pretreated advanced disease reported combined use of ipilimumab (anti-CTLA-4) with nivolumab (anti-PD-1) may have complementary action, thus yielding a highest clinical efficacy but is explored in heavily pretreated patients where immune resources could be altered. In addition, no strong biomarkers of efficacy have been reported. So exploring this combination seems an important option in the field of such aggressive disease for naïve patients.
Trial design
COLIBRI is a multicenter, single arm pilot study. Patients with histologically confirmed diagnosis of cervical squamous cell carcinoma stage IB3 to IVA will receive during induction phase (before RTCT), ipilimumab 1mg/kg once at D1C1 and nivolumab 3mg/kg at D1C1 and D15C1 and in maintenance phase (after RTCT) nivolumab monotherapy every 28 days at 480mg during 6 months. Tumor and blood samples will be collected at screening, after induction and after RTCT treatment periods. Additional samples will be scheduled during maintenance, if surgery is planned, at the end of treatment and at relapse. The main objective is to explore the impact on primary tumour and systemic immune response of nivolumab + ipilimumab combination before initial treatment. Enrolling 40 patients will provide a 95% CI with a precision of 5 units around the mean estimation of the CD8+/FOXP3+ lymphocyte ratio relative change from pre to post treatment biopsies, that could be considered as an early biomarker of the experimental treatments’ efficacy. Because of the high interpatient variability of CD8/FOXP3 ratio, we decided to consider a relative change from pre to post treatment. Secondary endpoints include safety, ORR, PFS, OS and biological endpoints to assess dynamic changes of the immune environment. Trial is currently recruiting; 31 patients were included and treated.
Clinical trial identification
EudraCT 2019-002271-34, NCT04256213.
Editorial acknowledgement
Legal entity responsible for the study
ARCAGY-GINECO.
Funding
ARCAGY-GINECO Bristol-Myers Squibb.
Disclosure
I.L. Ray-Coquard: Financial Interests, Personal, Other, Travel: AstraZeneca; Financial Interests, Personal, Other, Travel: GSK; Financial Interests, Personal, Other, Travel: Clovis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Advisory Board: Esai; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Onxena; Financial Interests, Personal, Advisory Board: Aravive. M. Kaminsky-Forrett: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Tesaro. F. Joly: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: Astellas; Non-Financial Interests, Institutional, Principal Investigator: GSK; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Research Grant: BMS. D. Bello Roufai: Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: ESAI; Financial Interests, Institutional, Invited Speaker: Lilly. A. Angelergues: Financial Interests, Personal, Invited Speaker: MSD. A. Hardy-Bessard: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Seagen. M.A. Mouret Reynier: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: Novartis. E. Deluche: Financial Interests, Personal, Other, Funding for conference travel: AstraZeneca-Daiichi; Financial Interests, Personal, Advisory Board: Fresenius-Kabi; Financial Interests, Personal, Other, Scientific events: GSK; Financial Interests, Personal, Other, Scientific events: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Funding for conference travel: Roche. C. Caux: Financial Interests, Personal, Other, honoraria: Janssen; Financial Interests, Personal, Other, honoraria: AstraZeneca; Financial Interests, Personal, Royalties: GSK; Financial Interests, Institutional, Funding: Servier; Non-Financial Interests, Institutional, Other, partnership: OSE Pharmaceutical; Non-Financial Interests, Institutional, Other, partnership: Celenion. P. Saintigny: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Inivata; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Board: HTG Molecular Diagnostics; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: OSE Immunotherapeutics; Financial Interests, Institutional, Research Grant: HTG Molecular Diagnostics; Financial Interests, Institutional, Research Grant: Illumina; Financial Interests, Institutional, Research Grant: Cellenion; Financial Interests, Institutional, Research Grant: Healthcare Company Hitachi; Financial Interests, Institutional, Research Grant: Vortex Biosciences; Financial Interests, Institutional, Research Grant: Inivata. H. Péré: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Janssen. F. Lecuru: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: Intuitive Surgery; Financial Interests, Personal, Invited Speaker: Oncoinvent; Financial Interests, Personal, Invited Speaker: Lilly. All other authors have declared no conflicts of interest.