Lung Master Protocol (Lung-MAP)—A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400

Abstract

The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell cancer (SCCA) of the lung. There are no approved targeted therapies specific to advanced lung SCCA, although The Cancer Genome Atlas (TCGA) project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCCA, some of which are targetable by investigational agents. However, the frequency of these changes is low (5–20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here we describe our approach to development of a biomarker-driven phase 2/3 multi-substudy “Master Protocol,” employing a common platform (Next Generation DNA Sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.

Incorporation of Next-Generation Sequencing into Routine Clinical Care to Direct Treatment of Head and Neck Squamous Cell Carcinoma

“…Early clinical development of novel HER2 and EGFR inhibitors, FGFR inhibitors, CDK inhibitors, and p53 modulators are all under way, and may be open to HNSCC patients who undergo appropriate genotyping studies. In the closely related disease, lung squamous cell carcinoma, genomic stratification for clinical trials is increasingly being adopted as evidenced by the recently initiated Lung-MAP study (26).…”

Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology-targeted drugs: a mapping of ClinicalTrials.gov

“…32 By contrast, "umbrella" trials such as NCI-MPACT 33 or SHIVA 34 tested multiple biomarkers across a broad range of tumor types. 35 In the open-label, controlled, phase II SHIVA trial, patients with metastatic solid tumor refractory to the standard of care and with a molecular alteration in phosphoinositide 3-kinase/AKT/mammalian target of rapamycin, RAF/MEK, or hormone receptor pathways were randomized to matched molecularly targeted agents in a histology-agnostic way and the physician's choice of treatment. There were no differences in primary outcome (progression-free survival) between the two groups: median progression-free survival was 2.3 months (95% confidence interval: 1.7-3.8) in the experimental group versus 2.0 months (1.8-2.1) in the control group (hazard ratio 0.88; 95% confidence interval: 0.65-1.19; P = 0.41).…”

Toward Personalized Targeted Therapeutics: An Overview

“…The 2 critical aspects of these new trial designs operate on the components of screening and treatment. For the screening component, patients are evaluated systematically for the presence of the biomarkers of interest, while in the treatment component, patients are assigned to substudies with investigational agents targeting the biomarkers present in their tumors [42]. The 2 primary clinical trial designs that exemplify this model are umbrella and basket trials.…”

“…Umbrella trials evaluate the impact of different drugs on different mutations in a single type of cancer. Examples of umbrella trials include BATTLE [43,44], Lung-MAP [42], and FOCUS4 [45]. In contrast, basket trials test the effect of 1 or more drugs on 1 or more single mutation in a variety of cancer types.…”

“…Examples of basket trials include NCI MATCH [46] and NCI IMPACT (NCT01827384). The design of umbrella and basket trials results in more efficient screening and facilitates the addition of new agents and biomarkers into the protocol on a rolling basis [42].…”