38: REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): a multi-arm phase II trial testing reduced intensity immunotherapy across different cancers
CRUK Clinical Research Fellow MRC CTU UCL London, England, United Kingdom
Background: Immune checkpoint inhibitors (ICI) have revolutionised the treatment of many advanced cancers. ICI are typically administered intravenously every 2-6 weeks until cancer progression or unacceptable toxicity. This requires a major commitment of resources for patients and health services. ICI have a long half-life and pharmacodynamic studies indicate sustained target occupancy despite falling levels of the drug. Therefore, extending the interval of administration should be possible without compromising outcomes. There are potential benefits to patients in terms of improved quality of life (QOL) and reduced toxicity and to healthcare services via lower resource use and costs.
Methods: REFINE is a multi-arm multi-stage (MAMS) phase II basket trial investigating extended interval administration of ICI across multiple cancer types. Eligible patients should have no evidence of progression after 12 weeks of ICI. REFINE is currently recruiting patients with locally advanced/metastatic renal cell carcinoma who have tolerated and responded to initial nivolumab/ipilimumab. In stage I, 160 patients will be randomised (in a 1:1 ratio) to receive SOC (nivolumab 480mg 4 weekly) vs extended interval (480mg 8 weekly). The primary outcome is progression free survival which will be analysed 6 months after completion of stage I recruitment. Subject to satisfactory outcomes, stage II will investigate up to 5 different treatment intervals. Secondary outcome measures include overall survival, QOL, toxicity and use of health care resources. Further cohorts including melanoma will open in the next 12 months. REFINE is recruiting across multiple sites in the UK. It 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. REFINE is running in parallel to REFINE-Lung which is coordinated by Imperial College.