Today, we have three versions of RANO and we should expect trials to reference elements of more than one of these criteria sets depending on the particular study agents:
The DCVax-L P3 trial did not useiRANOcriteria—it relied on conventional RANO guidelines.iRANOwas developed to addressimmunotherapy challenges like pseudoprogression, and is now being used in ongoing trials (such as the DCVax-L pembrolizumab combo) to improve response assessment accuracy.
iRANO’s refined methodology better distinguishes immune-related pseudoprogression from true tumor growth and enhances the accuracy of response assessments compared to earlier trials that used conventional RANO criteria.
As I mentioned, consider the example of the ongoing combo at UCLA for rGBM. This study is a combo with Merck’s pembrolizumab and RANO/iRANOis appropriately built into its design: