Abstract P1-14-03: The evaluation of trebananib plus standard neoadjuvant therapy in high-risk breast cancer: Results from the I-SPY 2 TRIAL
Authors: Albain KS , Leyland-Jones B , Symmans F , Paoloni M , van 't Veer L , DeMichele A , Buxton M , Hylton N , Yee D , Lyandres Clennell J , Yau C , Sanil A ,   I-SPY 2 Trial Investigators, Berry D , Esserman L 
Published: May 2016

Background: I-SPY 2 is a multicenter phase 2 trial using response-adaptive randomization within biomarker subtypes to evaluate a series of novel agents when added to standard neoadjuvant therapy for women with high-risk stage II/III breast cancer. The primary endpoint is pathologic complete response (pCR). The goal is to identify/graduate regimens with ≥85% Bayesian predictive probability of success (statistical significance) in a 300-patient phase 3 neoadjuvant trial defined by hormone-receptor (HR), HER2 status & MammaPrint (MP). Regimens may also leave the trial for futility (&lt; 10% probability of success) or following accrual of maximum sample size (10%&lt; probability of success &lt;85%). We report the results for trebananib, an angiopoietin-1/2-neutralizing peptibody that inhibits interaction with the Tie2 receptor.

Methods: Women with tumors ≥2.5cm were eligible for screening. MP low/HR+/HER2- tumors were ineligible for randomization. Serial MRI scans (baseline, 2 during treatment and pre-surgery) were used in a longitudinal model to improve the efficiency of adaptive randomization. Participants are categorized into 8 subtypes based on: HR status, HER2 status and MP High 1 (MP1) or High 2 (MP2). MP1 and MP2 are determined by a predefined median cut-point of I-SPY 1 participants who fit the eligibility criteria for I-SPY 2. Trebananib was initially assigned to HER2- patients only; once safety data with trastuzumab (H) were obtained, it was also assigned to HER2+ patients. Analysis was intent to treat -- patients who switched to non-protocol therapy were designated non-pCRs.

Results: Trebananib +/-H did not meet the criteria for graduation in any of the 10 signatures tested. When the maximum sample size was reached, accrual ceased. We report probabilities of trebananib +/-H being superior to control and Bayesian predictive probabilities of success in a 1:1 randomized neoadjuvant phase 3 trial for the 10 biomarker signatures, using the final pCR data from all patients.

SignatureEstimated pCR Rate (95% probability interval)Probability Trebananib Is Superior to ControlPredictive Probability of Success in Phase 3Trebananib (n=134)Control (n=133)ALL0.259(0.16 -0.36)0.158(0.09-0.23)0.9860.564HR+0.157(0.05-0.26)0.115(0.03- 0.20)0.8050.281HR-0.378(0.22-0.53)0.207(0.11- 0.31)0.9910.784HER2+0.279(0.07-0.49)0.17(0.04-0.30)0.8790.553HER2-0.254(0.15-0.36)0.155(0.08-0.23)0.9810.555MP20.342 (0.19-0.49)0.177(0.07-0.28)0.9910.786HR-/HER2-0.368 (0.21-0.53)0.201(0.10-0.30)0.9880.771HR-/HER2+0.444(0.15-0.74)0.244(0.07-0.42)0.9260.739HR+/HER2+0.201(0.01-0.39)0.135(0.01-0.26)0.7750.41HR+/HER2-0.143(0.04-0.24)0.11(0.03-0.19)0.7580.248

Citation Format: Albain KS, Leyland-Jones B, Symmans F, Paoloni M, van 't Veer L, DeMichele A, Buxton M, Hylton N, Yee D, Lyandres Clennell J, Yau C, Sanil A, I-SPY 2 Trial Investigators, Berry D, Esserman L. The evaluation of trebananib plus standard neoadjuvant therapy in high-risk breast cancer: Results from the I-SPY 2 TRIAL. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-03.