I-SPY 2 is a multicenter, phase 2 trial using response-adaptive randomization within biomarker subtypes to evaluate novel agents when added to standard neoadjuvant therapy for women with high-risk stage II/III breast cancer – weekly paclitaxel with an investigational treatment x 12 wk followed by doxorubicin & cyclophosphamide(AC) q3 wk x 4 vs. weekly paclitaxel/AC (control arm). The primary endpoint is pathologic complete response (pCR) at surgery. The goal is to identify/graduate regimens with ≥85% Bayesian predictive probability of success (i.e. demonstrating superiority to control) in a future 300-patient phase 3 1:1 randomized neoadjuvant trial with a pCR endpoint within signatures defined by hormone-receptor (HR) & HER2 status & MammaPrint (MP) result. Regimens may leave the trial for futility (< 10% probability of success), maximum sample size accrual (10%< probability of success <85%), or for safety as recommended by the independent DSMB. We report the results for an experimental arm.
Women with tumors ≥2.5cm were eligible for screening. MP low/HR+ were ineligible for randomization. MRI scans (baseline, 3 cycles after start of therapy, prior to AC, and prior to surgery) were used in a longitudinal statistical model to predict pCR for individual patients. Analysis was intention to treat with patients who switched to non-protocol therapy counted as non-pCRs. This investigational arm was open only to HER2- patients, and eligible for graduation in 3 of 10 pre-defined signatures: HER2-, HR+HER2- and HR-HER2-.
To be reported with placeholder update August 30, 2019.
The I-SPY 2 adaptive randomization study estimates the probability that investigational regimens will be successful in a phase 3 neoadjuvant trial. The value of I-SPY 2 is to give insight about the performance of an investigational agent’s likelihood of achieving pCR. We will report the results of an experimental arm August 30, 2019.