BATTLE-2: Next-Generation of Biomarker-Driven Trials
Roy S. Herbst, MD, PhD
Chief of Medical Oncology
Associate Director, Translational Research, Yale Comprehensive Cancer Center
Smilow Cancer Hospital at Yale-New Haven, Yale School of Medicine
New Haven, CT
Ignacio I. Wistuba, MD
Jay and Lori Eissenberg Professor in Lung Cancer, Director of the Thoracic Molecular Pathology Lab,
Departments of Pathology and Thoracic/Head & Neck
The University of Texas MD Anderson Cancer Center, Houston, TX
What is BATTLE-2 and why is it important?Herbst: The BATTLE-2 trial is a study that is designed to understand how tissue biomarkers predict who will respond to targeted therapy or targeted therapy combinations. The idea behind BATTLE is that every patient gets a biopsy at the time of their treatment so that it reflects the mutational status and biomarker status of their tumor, and then that information is used to put them onto one of four arms of the trial. In this case, the trial has an EGFR inhibitor (erlotinib); an inhibitor of Ras, Raf, and other [signaling molecules] (sorafenib); a combination of erlotinib plus an Akt inhibitor (MK-2206), which is thought to overcome EGFR resistance; and a combination to target KRAS,⎯a MEK inhibitor (AZD6244) plus an Akt inhibitor (MK-2206).
The way the BATTLE-2 trial works [is that] as soon as the patient has their new biopsy reflecting the tumor at the current time, it goes to Dr Wistuba’s lab. Within a week to 10 days his lab is able to provide a series of markers so we know what the profile is of that patient. Initially, the patients are equally randomized to each of the four arms, but as time goes by, as we learn how the marker profile predicts who does well, we start to adaptively randomize, meaning that they are more likely to get the arm that will benefit. So, this is an approach that the patients like because they’re not just being strictly randomized, but they’re being sorted based on their profile, and we’re learning. Dr Wistuba is also doing discovery work.
Wistuba: That’s the other important aspect—we use the information to assign the patients to the treatments, but we also use the tissue and the material that we have to potentially discover new things that could benefit future lung cancer patients. We are planning to take all this information and make clinical trials more specific based on what we are learning from these trials. So, it’s not just to assign patients based on the biomarker profile, but to discover new abnormalities in lung cancer that can help the entire field.
Herbst: Maybe 20%-30% of patients have a mutation or biomarker that can be used to give them a helpful therapy, but the other 70% don’t, so we’re going to learn by doing this work in a rigorous way with all the techniques that Dr Wistuba and his lab can employ. Dr Wistuba and I are doing this in collaboration with Dr Vassiliki Papadimitrakopoulou [University of Texas MD Anderson Cancer Center], and Dr J. Jack Lee [University of Texas MD Anderson Cancer Center]. We received an RO1 grant from the National Cancer Institute, so this is receiving peer-reviewed support.
Wistuba: We are also opening this at Yale, where Dr Herbst is now, so we’re going to show that this can be done in a multicenter way, because in the past it has been done at only one institution. By having this biopsy-driven trial in two places, I think this is also a step forward in the field.