Collaborative biomarker-driven Lung-MAP trial to test five approaches for NSCLC

A unique public-private collaboration has announced the initiation of Lung-MAP (Lung cancer MAster Protocol; ClinicalTrials.gov Identifier NCT02154490), a multidrug, multi-arm, biomarker-driven phase II/III trial for patients with recurrent stage IIIB-IV non-small cell lung cancer (NSCLC). The collaborators are the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), Southwest Oncology Group (SWOG) Cancer Research, Friends of Cancer Research, the Foundation for the National Institutes of Health (FNIH), Foundation Medicine and the companies Amgen, Genentech, Pfizer, AstraZeneca and AstraZeneca's global biologics R&D arm MedImmune. The aim is to improve access to promising drugs for patients and ease the significant recruitment and infrastructure burdens involved in traditional clinical trials. The trial will use genomic profiling to match patients to one of several different investigational treatments that are designed to target the genomic alterations driving the growth of their cancer. Lung-MAP will simultaneously test patients for many biomarkers, including selected base substitutions and small in/dels, gene fusions and amplifications, in order to assess compatibility with several different experimental treatments. It is anticipated that 500-1,000 patients will be screened per year for over 200 cancer-related genes for genomic alterations, with a total of 10,000 patients expected to take part. The results of this test will be used to assign each patient to the trial arm that is best matched to their tumor's genomic profile. The trial will initially test five experimental drugs: MEDI-4736, GDC-0032 (taselisib), palbociclib isethionate, AZD-4547 and rilotumumab. Patients with tumors that do not match one of the currently active drug-biomarker combinations will be randomized to MEDI-4736. Patients with tumors positive for phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) are randomized to GDC-0032. Patients with tumors positive for cyclin-dependent kinase (CDK) 4/6, CCND1, CCND2, and CCND3 will receive palbociclib isethionate. Subjects with tumors positive for fibroblast growth factor receptor 1 (FGFR-1), FGFR-2, and FGFR-3 will receive AZD-4547. Patients with tumors positive for hepatocyte growth factor (HGF)/c-MET will receive experimental rilotumumab and erlotinib hydrochloride. Within each patient subgroup, an active comparator of either docetaxel or erlotinib hydrochloride will be used. Primary outcome measures include progression-free survival (PFS) as defined by RECIST 1.1, a less than 33% improvement in median PFS as defined by RECIST 1.1, and overall survival. Secondary outcomes measures will include response rate (confirmed and unconfirmed) in patients with measurable disease as defined by RECIST 1.1, toxicity frequencies and PFS as defined by modified immune-related response criteria (irRC), and response rate as defined by irRC. Other outcome measures include screen success rate and treatment arm randomization acceptance rate. Lung-MAP uses a single master protocol, which can be amended as needed as drugs enter and exit the trial. The trial will be conducted at over 200 medical centers by NCI's National Clinical Trials Network (NCTN), led by SWOG, and partly funded by NCI through its Cancer Therapy Evaluation Program. The trial infrastructure is capable of testing as many as 5-7 additional drugs over the next 5 years, and will cost up to USD 160 million. The study is expected to be completed in June 2022.