Two of the most innovative lung cancer focused clinical studies launched recently, the Lung Cancer Master Protocol (Lung-MAP) and the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST), have been the result of a National Cancer Institute (NCI) sponsored workshop chaired by Drs. Fred R. Hirsch, Shakun Malik and Claudio Dansky-Ullman. Both researchers were able to gather the NCI Thoracic Malignancies Steering Committee, the US Food and Drug Administration (FDA), academicians, clinicians as well as industry and government stakeholders to discuss some of the problems of clinical trial design and biomarkers for lung cancer targeted-therapies.
The objective of this workshop was to enable fruitful collaborations that could help design a high priority biomarker-driven clinical study to assess the efficacy of a targeted-therapy in a specific lung cancer population, while helping to collect data for regulatory approval.
The results of the workshop were published in the October issue of the Journal of Thoracic Oncology, and highlight the different types of biomarkers, clinical trial designs and possible primary endpoints for these trials, along with regulatory challenges concerning drug development, biomarker development, and the necessary data needed for drug approval.
The Lung-MAP trial was launched last June and is a collaboration between the NCI, the “Friends of Cancer” organization, the Southwest Oncology Group (SWOG) thoracic oncology committee, Foundation Medicine, the Foundation for the National Institutes of Health, and five pharmaceutical companies (Amgen, Genentech, Pfizer, AstraZeneca, and AstraZeneca’s global biologics R&D arm, MedImmune). This trial screens patients suffering from advanced lung squamous cell carcinoma using a genomic profiling platform that examines over 200 cancer-related genes for genomic alterations. Patients are then assigned to one of the five different investigational therapies that best match their genomic profile.
The ALCHEMIST trial began in August and is a combination of three component trials for early stage non-squamous lung cancer that has been surgically resected. The patient’s tumor tissue is then tested for EGFR mutations and ALK rearrangements along with other possible genomic abnormalities at disease recurrence, and the patients assigned to the treatment that best fits their type of tumor.
“The concept of a “Master protocol” in lung cancer is unique for rapid identification of active drugs and a rapid pathway to drug approval based on predetermined efficacy parameters. It is a unique public-private partnership, which rapidly should lead to offering the many desperate lung cancer patients a long awaited hope. The Master Protocol concept is now a role model for other tumor types, such as colorectal cancer, where similar trials are planned,” Dr. Hirsch, chair for the workshop and Chief Executive Officer of the International Association for the Study of Lung Cancer (IASLC), said in an IASLC press release.