In a new biomarker-focused clinical trial, five therapies will be tested to develop new, precision medicine approaches to treat squamous cell lung cancer.
In a new biomarker-focused clinical trial, five therapies will be tested to develop new, precision medicine approaches to treat squamous cell lung cancer. The Lung Cancer Master Protocol (Lung-MAP)/SWOG S1400 phase 2/3 clinical trial, brings together the National Cancer Institute (NCI), the Foundation for the National Institutes of Health (FNIH), SWOG Cancer Research, five pharmaceutical companies (Amgen, AstraZeneca, Genentech, MedImmune, and Pfizer), Foundation Medicine (a molecular informatics company), and Friends of Cancer Research, a non-profit foundation.
The trial aims to enroll about 10,000 patients total and will cost about $160 million, of which the NCI is contributing $25 million.
Lung-MAP is unique as this is the first public-private partnership in drug development that includes the National Cancer Institute (NCI), the US Food and Drug Administration (FDA), US oncology cooperative groups, and a number of patient advocacy groups according to one of the study investigators, David Gandara, MD, chair of the SWOG lung committee, and thoracic oncologist at the UC Davis Cancer Center. “Funds are made available for every aspect of the trial,” said Gandara. “There is nothing in the history of oncology or drug development like it.”
The clinical trial seeks to identify molecular aberrations in patients with advanced squamous cell lung cancer that can be targeted either by existing therapies or through the development of new ones. The innovation of this trial is a master protocol that will rely on the strength of numbers-up to 1000 patients per year at more than 200 sites throughout the US for more than 200 cancer-related genetic alterations. Testing results will then dictate which experimental trial arm is most appropriate for which patient. Unlike a trial that seeks to enroll patients harboring just one mutation, which limits the access for many patients, the Lung-MAP design better ensures that a patient who is screened will be eligible for a targeted therapy trial arm.
This type of umbrella trial design is particularly suitable for squamous cell lung cancer. Thus far, has not been defined by one or several driver mutations. Instead, these tumors are made of a spectrum of genetic aberrations that are each relatively rare within the squamous lung cancer patient population, making enrollment into targeted therapy clinical trials difficult. According to the NCI, Lung-MAP “aims to establish a model of clinical testing that more efficiently meets the needs of both patients and drug developers," facilitating more efficient matching of a patient to an investigational targeted therapy trial.
Lung-MAP was specifically designed for squamous cell lung cancer because this lung cancer subtype represents the greatest unmet need for new treatment, Gandara told OncoTherapy Network:
“All of the dramatic advances that have been made in the treatment of lung cancer over the last ten years have occurred in adenocarcinoma, a lung cancer subtype with several recently recognized and ‘druggable oncogenes’ such as EGFR mutations or ALK translocations. However, there have been essentially no advances in squamous cell lung cancer.”
But, recent genome-wide studies have identified several gene alterations in squamous cell lung cancer that are also druggable, including PI3K, FGFR, and CDK mutations, said Gandara. The trial is initially testing four targeted therapies: Genentech’s GDC-0032 (a PI3 kinase inhibitor), Pfizer’s palbociclib (an oral cyclin-dependent-kinase 4/6 inhibitor, AZD4547), an oral fibroblast growth factor receptor inhibitor from AstraZeneca, and rilotumumab, Amgen’s antibody against the human hepatocyte growth factor.
The fifth agent is, MEDI4736, an immune checkpoint inhibitor antibody targeting PD-L1. Patients whose tumors do not harbor a mutation suitable for targeting with one of the four targeted therapies will be enrolled in the MED4736 sub-study.
Once a patient is matched to a specific trial sub-study, randomization will determine whether the patient receives the experimental therapy or standard of care chemotherapy. The planned trial endpoints for each sub-study are overall survival and progression-free survival.
“I cannot overemphasize the importance of the FDA’s participation in this project, since each of these sub-studies is designed to result in approval of a paired biomarker and new drug if that sub-study meets the requirements for improved effectiveness,” said Gandara.