The I-SPY Trials

PHASE I: I-SPY Phase 1

The I-SPY Phase 1 program was developed to help pharmaceutical companies and investigators meet the safety qualifications necessary for participation in I-SPY 2 and/or I-SPY 3 Trials.

Similar to all Phase I clinical trials, I-SPY Phase 1 is designed to determine drug safety.  Additionally, it is designed to decrease the amount of time required to collect drug safety data. This is done using innovative processes designed to reduce timelines including:

• A master contract,

• Template protocols,

• I-SPY Phase 1 network sites, which allow accelerated expansion cohort enrollment, and provides earlier feedback for the preparation and inclusion of the agent in I-SPY 2 and I-SPY 3 protocols.

The I-SPY Phase 1 network is comprised of seven trial locations. With each new phase 1 study, one site will serve as the lead with additional sites joining the expansion phase, as needed.  

I-SPY Phase 1 Trial Sites:


The focus of I-SPY 2 TRIAL is on treating patients with stage 2-3 breast cancer at the time of primary diagnosis and therefore at the highest risk of progression. Patients are being accrued at 16 clinical study sites around the U.S. and Canada

I-SPY 2 represents an unprecedented re-engineering of the clinical trial design process for Phase II clinical trials. Similar to all Phase II clinical trials I-SPY 2 is designed to determine safety and efficacy of new treatments. However, by incorporating a number of highly innovative and unique features, the I-SPY 2 TRIAL is also designed to decrease the time, the cost, and the number of patients required to efficiently bring new drug therapies to breast cancer patients who need them urgently.  

Five critical components contribute to the I-SPY 2 groundbreaking approach:

NeoaDJUVant Chemotherapy

Administration of chemotherapy prior to surgery and use of MRI to track tumor response to treatment.



Utilizes the response information from each patient as she goes through the study to help in treating the next patients.

Personalized treatment

Using the patient's tumor profile to assign targeted therapies best suited to her tumor biology.


An adaptive standing platform trial enables testing of multiple agents, creates efficiency within the trial, and allow drugs to be evaluated faster.


Allows data to be collected, verified and shared real-time — enhancing and encouraging pre-competitive collaboration.

Fine Tuned primary endpoint

Use of pathological complete response (pCR) - the absence of residual invasive disease as an early surrogate marker of longer-term outcomes of relapse-free and overall survival.


I-SPY 2 Pharma Partners

The I-SPY 2 TRIAL collaborates with multiple pharmaceutical companies.

I-SPY 2 Trial Sites

Washington DC



The I-SPY 3 TRIAL is an international confirmatory trial of successful agents who have graduated from the I-SPY 2 TRIAL. Similar to all Phase III clinical trials, I-SPY 3 is designed to confirm the efficacy of new treatments. However, the goal of the I-SPY 3 TRIAL is to accelerate the phase III testing of agents through a variety of mechanisms including:

• Targeted eligibility criteria for subtypes of breast cancer most likely to respond

• Serial interim analyses to allow for informed and efficient decision making

• Adaptive design to optimize sample size determination and maximize potential for success

• Reducing the number of patients required

Similar to the I-SPY 2 TRIAL design, the I-SPY 3 TRIAL is a standing trial consisting of a master protocol and IND with shared control arms aimed to reduce time and costs. The trial also utilizes parallel approval pathways for US Food and Drug Administration (FDA) and European Medicines Agency (EMA) and is currently developing a novel IT infrastructure to support the trial.

The I-SPY 3 TRIAL consortium works with sites across the European Union, Australia, New Zealand, Canada, and Japan, with a focus on partnering with high accruing sites to reduce time and costs. Academic Research Organizations (ARO) also play an important role in the trial by contributing clinical trial expertise, local and regional knowledge, and global reach. The trial leverages and combines best practices from these groups as well as the trial’s Clinical Research Organization (CRO).


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