Abstract 782TiP
Background
Immune checkpoint inhibitors (ICI) have revolutionised cancer treatment, resulting in long-term durable responses. In advanced disease, ICIs are administered every 2-6 weeks i.v. until cancer progression or unacceptable toxicity, which is often several years’ treatment. Physiological efficacy of anti-PD-1 antibodies (maximal receptor occupancy) is seen at lower doses than those in routine use. Pharmacodynamic studies indicate sustained target occupancy of >70% for at least 2 months, despite half-lives of 2-3 weeks. Therefore reducing the frequency of administration should be possible without compromising outcomes. REFINE tests limiting individual patient exposure to ICI whilst maintaining efficacy, with potential benefits in quality-of-life (reduced toxicity and fewer hospital visits) and lower drug treatment and attendance costs.
Trial design
REFINE is a randomised phase II, multi-arm, multi-stage (MAMS) adaptive basket trial investigating extended interval administration of ICIs. Eligible patients are those responding (radiologically) to ICI at 12 weeks. In stage I, patients (n= 160 per tumour-specific cohort) will be randomly allocated (1:1) to receive maintenance ICI at SOC vs extended dose interval. REFINE is currently recruiting patients with locally advanced or metastatic renal cell carcinoma who have received treatment with ipilimumab plus nivolumab. They will be randomised to receive maintenance nivolumab as SOC (480mg 4 weekly) vs extended interval dosing (480mg 8 weekly). Additional tumour cohorts will be opened shortly. Disease control will be analysed 6 months from completion of stage I recruitment and inform stage II, which will investigate up to 5 different treatment intervals. The primary outcome measure for both stages is progression-free survival. Secondary outcome measures include overall survival, quality-of-life, treatment-related toxicity and mean incremental pathway costs and quality-adjusted life-years per patient. REFINE will recruit across the UK. The trial is funded by the Jon Moulton Charity Trust and Medical Research Council, sponsored by University College London (UCL), and coordinated by the MRC CTU at UCL.
Clinical trial identification
NCT04913025.
Editorial acknowledgement
Legal entity responsible for the study
Medical Research Council Clinical Trials Unit at University College London.
Funding
Jon Moulton Charity Trust and Medical Research Council.
Disclosure
L.M. Pickering: Financial Interests, Personal, Invited Speaker: EISAI, Ipsen, Pfizer; Financial Interests, Personal, Advisory Role: BMS, EUSA Pharma, Pfizer, MSD. N.S. Vasudev: Financial Interests, Personal, Invited Speaker: BMS, Ipsen, EUSA Pharma; Financial Interests, Personal, Advisory Role: BMS, Merck, Pfizer, 4D Pharma; Financial Interests, Institutional, Research Grant: BMS. All other authors have declared no conflicts of interest.