I-SPY 2.2

I-SPY 2.2 began in 2022 under the same registration as I-SPY 2. It replaces the fixed backbone with three blocks. Block A gives an experimental treatment matched to the tumour's response-predictive subtype (defined by hormone receptor, HER2, an immune signature and a DNA repair deficiency signature). Women whose MRI and biopsy show the tumour has gone go straight to surgery; the rest move to block B, standard chemotherapy or a subtype-specific standard, and if still not responding to block C, the best current treatment for that subtype. The design is a sequential multiple assignment randomised trial, so each woman's path is set by her own early response.

The aim is to raise the pathological complete response rate while lowering the amount of chemotherapy given, and to find, for each subtype, the treatment that works alone. Early results reported from 2024 have described complete response rates by block for the first experimental agents and the share of women who could avoid the chemotherapy blocks altogether.