Biomarkers Consortium – I-SPY TRIAL-2 (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and MoLecular Analysis): An Adaptive Breast Cancer Trial Design in the Setting of Neoadjuvant Chemotherapy


The I-SPY 2 trial was setup to accelerate the pace of qualifying effective novel agents for breast cancer by testing new agents in high-risk women with locally advanced (Stage 2 and 3) newly diagnosed breast cancer in the neoadjuvant setting. The trial used extensive biomarker testing and an adaptive design, with intermediate markers (complete pathologic response (pCR), MR imaging, and biomarkers) as a way to measure drug efficacy and move successful regimens and biomarkers to focused phase III trials. This project involves collaboration from all sectors including Food and Drug Administration scientists, National Cancer Institute scientists, clinical trialists, industry, and patient advocate groups.


  • Phase II trial of novel investigative breast cancer agents in the neoadjuvant setting that uses biomarkers and adaptive design to accelerate the clinical trial process.
  • Using biomarkers from individual patients’ tumors to screen promising new treatments, identifying which treatments are most effective in specific types of patients.
  • Utilizing an adaptive trial design enables Researchers to use early data from one set of patients to guide decisions about which treatments might be more useful for patients later in the trial, while minimizing the exposure of patients to treatments that do not benefit them.

Results & Accomplishments

Completed Phase II testing on eleven drugs (neratinib, veliparib, AMG386, ganitumab, MK2206, pertuzumab, TDM1+pertuzumab, ganetespib, PLX3397, patritumab, and pembrolizumab) to date. Three of these trials were completed and did not proceed to a Phase III in this clinical setting (AMG386, ganitumab, and ganetespib). Two of these drugs were halted during the Phase II study (PLX3397 and patritumab), and the remaining six drugs graduated to Phase III (neratinib, veliparib, MK2206, pertuzumab, TDM1+pertuzumab, and pembrolizumab). An addition four drugs have been added to the trial and are currently in Phase II testing (talazoparib, SGN-LIV1A, and durvalumab+olaparib).


Public-Sector Partners:

  • National Cancer Institute (NCI)
  • U.S. Food and Drug Administration (FDA)

Private-Sector Partners:

  • Abbott*
  • Alexandria Real Estate Equities, Inc.*
  • Amgen, Inc.*
  • Avon Foundation for Women*
  • Buffy M Cafritz*
  • Edge Hill Inc.*
  • Eisai Inc.*
  • Genentech, a member of the Roche Group*
  • Johnson & Johnson*
  • Susan B Komen Foundation*
  • Eli Lilly and Company*
  • Merck Sharp & Dohme Corp.*
  • Pfizer Inc.*
  • QuantumLeap Healthcare Collaborative*
  • Quintiles Transnational Corporation*
  • The Safeway Foundation*
  • The Edmond J. Safra Philanthropic Foundation*
  • The Side-Out Foundation*

Academic Partners:

  • MD Anderson Cancer Center
  • University of California-San Francisco

*Provided financial or in-kind support for this program.

FNIH Contact

Scientific Publications

Data Access


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