The Phase III failure of the first targeted therapy to graduate from I-SPY 2 does not mean the platform trial wasn’t able to predict the correct outcome. What it does mean is that I-SPY 2 cannot distinguish the relative contributions of the components of a novel combination regimen -- which isn’t what it was designed to do anyway.
According to I-SPY 2, adding the combination of veliparib from AbbVie Inc. and carboplatin to standard of care had an 88% chance of significantly increasing pathologic complete response (pCR) over SOC alone in a Phase III trial in neoadjuvant triple-negative breast cancer (TNBC).
Detailed results of a subsequent Phase III study from AbbVie that were presented at the American Society of Clinical Oncology (ASCO) meeting on June 4 showed the combination did improve pCR over SOC -- it’s just that all the benefit came from carboplatin, while veliparib made no contribution at all.
“They saw a signal, but it wasn’t from the drug we had hoped it would be from,” Laura Esserman told BioCentury.
Esserman is lead PI on I-SPY 2, director of the UCSF Carol Franc Buck Breast Care Center and the co-leader of the breast oncology program at the UCSF Helen Diller Family Comprehensive Cancer Center.
“They saw a signal, but it wasn’t from the drug we had hoped it would be from.”
The implications for the current I-SPY study and similar platform trials are that combinations ought to have some clinical evidence of efficacy -- and synergy -- before they are tested in a platform study.
For the future, the I-SPY PIs are working on a new trial protocol that takes a more stepwise approach to untested combinations by allowing patients who don’t respond to monotherapy to be re-randomized to receive an additional component to get them to