Vassiliki Papadimitrakopoulou, MD
Five novel agents for the treatment of patients with advanced squamous cell carcinoma of the lung will be evaluated in the recently launched Lung-MAP trial, an innovative biomarker-driven study that aims to improve the drug development process while exploring therapeutic options for this challenging malignancy.
Plans call for enrolling up to 5000 patients through more than 200 medical centers during the next five years in randomized phase II substudies of the novel agents after participants have been screened through a master protocol. The study, formally known as SWOG S1400, may cost up to $160 million and involve testing an additional five to seven drugs beyond the agents initially selected, Lung-MAP organizers said in announcing the study in June.1
The first round of agents to be tested include four targeted therapies—GDC-0032, palbociclib, AZD4547, and rilotumumab—and the immunotherapy MEDI4736.2
The logistics of the trial have been challenging to coordinate but academic researchers, government regulators, and pharmaceutical companies have embraced the concept, according to Vassiliki Papadimitrakopoulou, MD, the principal investigator. Collaborators include six companies, the SWOG and the National Clinical Trials Network research cooperatives, and the National Cancer Institute (NCI).
“Everybody sees the advantages in the process. We have an unprecedented willingness to participate,” said Papadimitrakopoulou, a professor in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston.
“There is a realization that we’re doing things in such a fractional way in clinical research now that we’re not really fulfilling our goals of getting safe and effective drugs to the patients as fast as possible,” she said.
Papadimitrakopoulou discussed the Lung-MAP trial in a telephone interview with OncLive
in advance of the 15th Annual International Lung Cancer Congress, where she will explain the use of the master protocol design for implementing personalized medicine. Physicians’ Education Resource (PER) is hosting the conference July 31-August 2 in Huntington Beach, California.
Key Facets of the Trial
The Lung-MAP trial seeks to recruit patients with advanced or incurable stage IIIB/IV squamous cell carcinoma who have progressed after receiving one frontline platinum-containing chemotherapy regimen for metastatic disease (Table
). Detailed criteria for assignment to a substudy group and then to a study drug also have been developed.2
To screen for biomarkers, investigators will conduct genomic profiling on either archived or freshly obtained tumor specimens using the FoundationOne test, which analyzes 182 genes.
After genomic evaluation, patients will be channeled into one of five substudies depending on their biomarker status and then randomized within that study. The substudies are:
MEDI4736 versus docetaxel—Participants whose tumors do not harbor any of the targeted alterations will be randomized to receive either MEDI4736, a monoclonal antibody directed against the programmed death ligand-1 (PD-L1), or the standard chemotherapy docetaxel. MedImmune, a research arm of AstraZeneca, is developing the immunotherapy agent.
GDC-0032 versus docetaxel—Patients whose tumors test positive for a PI3KCA mutation will receive either GDC-0032 or docetaxel. GDC-0032, a beta-isoform-sparing PI3K inhibitor, is an oral agent from Genentech.
Palbociclib versus docetaxel—Individuals whose tumors test positive for CDK4/6 or CCDN1/2/3 amplification will be randomized for treatment with either palbociclib or docetaxel. Palbociclib is a small molecule from Pfizer that has gained Breakthrough Therapy status in breast cancer.
AZD4547 versus docetaxel—Participants whose tumors harbor alterations in FGFR1/2/3 will be given either AZD4547 or docetaxel. AZD4547 is a tyrosine kinase inhibitor that AstraZeneca is developing.
Rilotumumab plus erlotinib versus erlotinib—Patients whose tumors have HGF/c-MET mutations will receive rilotumumab intravenously on day 1 and erlotinib daily, versus erlotinib daily. Rilotumumab is a monoclonal antibody in Amgen’s pipeline that inhibits hepatocyte growth factor activity. Erlotinib (Tarceva) is an EGFR inhibitor approved in several lung cancer settings, including as a second-line treatment for patients who progress after chemotherapy.
Papadimitrakopoulou said 16 pharmaceutical companies competed to have their drugs included in the trial in a rigorous process that included presenting data before a selection committee.