Abstract No. 
2019 San Antonio Breast Cancer Symposium
December 10-14

Evaluation of a pembrolizumab-8 cycle neoadjuvant regimen without AC for high-risk early-stage HER2-negative breast cancer: Results from the I-SPY 2 TRIAL

Liu MC, Robinson PA, Yau C, Wallace AM, Chien A, Stringer-Reasor E, Nanda R, Yee D, Albani KS, Boughey JC, Han HS, Elias AD, Kalinsky K, Clark AS, Kemmer K, Isaacs C, Lang JE, Lu J, Sanft T, DeMichele A, Hylton NM, Melisko ME, Perlmutter J, Rugo HS, Schwab R, Symmans W, van 't Veer LJ, Haugen PK, Wilson A, Singhrao R, Asare S, Sanio A, Berry DA, Esserman LJ


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.  

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