119IN - Novel molecular studies to inform the conduct of oncology clinical trials: From Battle to Master Protocols

Date 29 September 2014
Event ESMO 2014
Session ESMO-ASCO: The evolution of the clinical trial landscape
Topics Bioethics, Legal, and Economic Issues
Translational Research
Presenter Roy S. Herbst
Citation Annals of Oncology (2014) 25 (suppl_4): iv41-iv42. 10.1093/annonc/mdu317
Authors R.S. Herbst
  • Comprehensive Cancer Center, Yale School of Medicine, 06520 - New Haven/US




Cancer is the second leading cause of death in the United States. Systemic chemotherapy is a mainstay and although therapies have improved, most patients with metastatic disease will eventually succumb to the disease. Identification of potential therapies is often based on subjective physician preference and clinical characteristics such as age, gender, or performance status. However, paradigm shifts are occurring with the emergence of tumor biomarkers as a key factor in the identification of therapies that can slow or reverse the growth of an individual patient's cancer. To remain competitive, new therapies that are being developed must also produce a viable tumor marker that can be used to identify ideal candidates for the therapy. Several new trials have been designed with this dual purpose in mind, particularly in the lung cancer arena. The BATTLE program represents the next generation paradigm for clinical trials research. BATTLE-2 combines a trial to identify the most effective treatment regimens for lung cancer patients in real time with a parallel biomarker discovery effort. This multicenter Phase 2 trial with adaptive randomization design will be a model for future studies. Furthermore, developed through an unprecedented collaboration between advocates, government, academia, and industry, the Lung-Map trial will be the mechanism to genomically screen a large population of squamous cell lung cancer (SCLC) patients to subsequently assign and accrue simultaneously to a multi-sub-study “Master Protocol” prospective, randomized phase 2/3 registration protocol. The Lung-Map trial will focus on testing drugs driven by the presence of biomarkers in the study population. This “umbrella” type trial will evaluate different targeted therapies/biomarker combinations in a single type of cancer. This grouping of biomarker driven targeted drug studies under a single protocol will reduce the screen failure rate, reduce operational and protocol development redundancies and improve efficiency and provide a consistent protocol that can be used to test multiple therapies. Using this approach it is hoped that new targeted agents will be tested and available in the community setting, in a trial design which will allow for a rapid assessment of efficacy and drug approval if the data are supportive.


R.S. Herbst: Science Advisory Board for: Biothera, DiaTech Oncology, N of One, Kolltan.