CLINICAL TRIALS

I-SPY2.2 Trial for Early Breast Cancer

Building on the success of I-SPY2, the I-SPY consortium, in collaboration with QLHC, have once again re-engineered the clinical trial, maintaining its focus on efficiency while permitting the optimization of treatment for each individual patient in the context of patient-friendly, phase II drug development.

Like its predecessor, I-SPY2.2 uses the neoadjuvant treatment approach. The primary endpoint remains pCR, and is supplemented by secondary endpoints including Residual Cancer Burden (RCB) and a combined efficacy/toxicity score.

Features include:

Platform Design

The adaptive platform approach permits parallel evaluation of multiple experimental treatments. A master protocol means treatments can come and go as they finish testing.

Response Monitoring

Serial MRIs are used to closely monitor the impact of treatment on the tumor at multiple points before, during and after treatment. MRI can routinely predict whether complete response has been achieved.

Biological Targeting

I-SPY2.2 uses molecular response-predictive subtypes to characterize each participant's tumor in order to guide treatment assignments and assess subtype-specific efficacy of treatment.

Treatment Redirection

If an experimental therapy does not work, participants are switched to an established, biologically targeted therapy. Participants may receive up to 3 blocks of treatment in I-SPY2.2.

Treatment Sparing

Participants get no more treatment than needed to achieve a complete response, in order to limit side effects of unnecessary treatment. A key goal is to eliminate traditional chemotherapy.

Treatment Strategies

In addition to assessing experimental agents, I-SPY2.2 assesses whole treatment strategies consisting of multiple sequential treatments, more closely reflecting clinical approaches.

1/4 Control Arm

One in five participants in I-SPY2.2 are randomized to a control arm that parallels the experimental arm, but omits the initial treatment block using experimental therapies.

Biomarker Rich

Complementing I-SPY's novel clinical design is a comprehensive biomarker discovery and validation program, open to third-party investigators with novel ideas.

Continuous Learning System

As a continuously operating trial, I-SPY is able to readily improve outcomes in early breast cancer by handling lesser-known treatments and enabling rapid, evidence-based clinical decision-making.

How it works:

I-SPY2.2 integrates a sequential multiple assignment randomized trial into the adaptive platform design. Imaging tools developed over the 10-year course of I-SPY2 allows longitudinal monitoring of tumor response that guide the course of treatment with rules-based algorithms. Patients demonstrating a complete response after a course of therapy can forgo further systemic treatment and undergo definitive surgery. Participants with suboptimal response to one therapy are given the option of receiving a different, biologically targeted therapy matched to their tumor type or a more traditional, rescue therapy prior to surgery. The result is the ability to optimize individual patient outcomes and minimize drug exposures to limit side effects, while identifying new agents and combinations that have a high probability of impacting future care.

Who is it for?

I-SPY2.2 is open to adults age 18 or older with stage II or III early breast cancer at high molecular risk of recurrence. Women with HR+/HER2- disease at low risk of recurrence may be eligible to participate in the I-SPY Endocrine Optimization Protocol trial.

Clinical Sites

I-SPY2.2 operates at participating sites across the United States, including OHSU, UCSF, UC Davis, Hoag Institute, USC, City of Hope, UCSD, Huntsman, UC Denver, Mayo Clinic, U Minnesota, Henepin County MC, Loyola, Silver Cross, Gottlieb Memorial, U Rochester, Roswell Park, Cooperman Barnabas, Yale, NYU Langone, Columbia, Rutgers, UPenn, Georgetown, MedStar Wash, Wake Forest, UAB, Emory, Moffitt, U Miami, Ohio State, and UChicago.

Funding

I-SPY2.2 is funded by the National Cancer Institute of the National Institutes of Health (NIH) under award number P01CA210961, and a number of generous donors. If you are interested in supporting I-SPY2.2, please see our giving pages.

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