Consensus report of a joint NCI thoracic malignancies steering committee: FDA workshop on strategies for integrating biomarkers into clinical development of new therapies for lung cancer leading to the inception of "master protocols" in lung cancer

Abstract

On February 2, 2012, the National Cancer Institute (NCI) sponsored a 2-day workshop with the NCI Thoracic Malignancies Steering Committee and the Food and Drug Administration to bring together leading academicians, clinicians, industry and government representatives to identify challenges and potential solutions in the clinical development of novel targeted therapies for lung cancer. Measures of success are rapidly evolving from a scientific and regulatory perspective and the objectives of this workshop were to achieve initial consensus on a high priority biomarker-driven clinical trial designed to rapidly assess the activity of targeted agents in molecularly defined lung cancer subsets and to facilitate generation of data leading to approval of these new therapies. Additionally, the meeting focused on identification of the barriers to conduct such a trial and the development of strategies to overcome those barriers. The "Lung Master Protocols" recently launched by NCI were the direct outcome of this workshop.

FIGURE 1.

ALCHEMIST study schema. ALCHEMIST—A151216, screening trial; ALCHEMIST—EGFR A081105, erlotinib treatment arm; ALCHEMIST—ALK E4512, crizotinib treatment arm.

FIGURE 2.

Phase II/III biomarker-driven master protocol for second-line therapy of squamous cell lung cancer (Lung-MAP Trial). *Archival formalin-fixed paraffin-embedded (FFPE) tumor, fresh core needle biopsy if needed. **CT = chemotherapy (docetaxel) control arm. ***E = erlotinib control arm. ****Substudy assignment will be determined based on randomization for patients eligible for multiple substudies.