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MO18 - NSCLC - Targeted Therapies IV (ID 116)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
MO18.08 - Phase II/III Biomarker-Driven Master Protocol for Second Line Therapy of Squamous Cell Lung Cancer (SCCA). (ID 1958)
16:15 - 17:45 | Author(s): I. Wistuba
There are few new effective therapeutic options for patients with advanced, lung SCCA; overall survival for metastatic disease being less than one year. The Cancer Genome Atlas (TCGA) project and similar studies have detected a significant number of somatic gene mutations/amplifications in patients with this disease, some of which are targetable by investigational agents. However, the frequency of these changes is low (5-20%) in these patients, making recruitment and treatment very challenging in the traditional single-agent trial setting. Our approach is to use a common platform (Next Generation DNA Sequencing) to enable a single “umbrella screening protocol” to efficiently find patients with varied, uncommon molecular changes.
Figure 1 This is a prospective, multi-substudy randomized Phase II/III Master Registration Protocol in which patients with advanced stage Lung SCCA (2[nd] line therapy)are randomized to biomarker-driven targeted therapy (TT) or standard of care (SOC) as shown in the schema after undergoing genomic screening. Genomic screening of a large patient resource provided by sites participating in the NCI North American Intergroup will identify molecular targets/biomarkers with an analytically validated diagnostic assay and a new drug match, leading to appropriate drug treatment-arm assignment. Archival FFPE tumor and/or core needle biopsies will be screened by a broad analytically validated next generation sequencing (NGS) platform centrally to establish eligibility within 10-14 days. This platform will be supplemented by individual immune-histochemical (IHC) protein assays performed in a CLIA setting as necessitated by the specific experimental agent used. Patients will be screened with homogeneous eligibility criteria. The overall trial objective is to establish a mechanism to genomically screen large but homogeneous cancer populations and subsequently assign and accrue simultaneously to multiple substudies comparing new TT to SOC therapy based on the identified therapeutic biomarker-drug combination. Each sub-study will function autonomously and will open and close independently of the other sub-studies. Drug combinations in the experimental arm will be allowed in appropriate settings and where appropriate the control arm may consist of FDA approved targeted therapy such as erlotinib. Each sub-study is independently powered for OS with an interim analysis for PFS to determine the “go-no go” decision to proceed from Phase II into Phase III. Each agent, along with the paired biomarker, that is successful at the interim analysis based on PFS will advance to a Phase III randomized registration trial (on behalf of the Master Protocol Steering Committee).
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