A phase II randomized open-label study for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutation, will test the EGFR inhibitor osimertinib with or without ramucirumab.

The study, HCRN LUN18-335, is now open to accrual at The University of Texas MD Anderson Cancer Center in Houston; Columbia University Irving Medical Center in New York; Fred Hutchinson Cancer Research Center in Seattle; Georgetown Lombardi Comprehensive Cancer Center in Washington, DC; Indiana University Melvin and Bren Simon Comprehensive Cancer Center in Indianapolis; Moffitt Cancer Center in Miami; New York University Cancer Institute in New York; Providence Cancer Institute in Portland, Oregon; Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago; Rush University Medical Center in Chicago; Summit Health Cancer Center in Florham Park, New Jersey; and the University of Virginia Cancer Center in Charlottesville, Virginia.

EGFR is a protein on the surface of cells, which help cells grow and divide. When NSCLC cells have too much EGFR, however, they can grow very quickly. EGFR inhibitors such as osimertinib can block the signal from this EGFR gene to stop cells from growing. These drugs can often shrink tumors for several months. However, most EGFR lung tumors stop responding to EGFR inhibitors and eventually start growing again. Sometimes these tumors don’t respond anymore because of an increase in other types of proteins, such as vascular endothelial growth factor (VEGF).

In a healthy body, VEGF signaling helps new blood vessels form in a process called angiogenesis. However, in EGFR lung cancers, VEGF levels increase and promote tumor growth, and make EGFR inhibitors unresponsive. To combat this, a VEGF inhibitor, ramucirumab, blocks new blood vessel growth. This drug, which is a monoclonal antibody, helps stop the formation of new blood vessels.

Osimertinib is approved by the U.S. Food and Drug Administration (FDA) to treat lung cancer with EGFR mutations. Ramucirumab has been approved by the FDA to treat lung cancer in combination with chemotherapy.

The combination of osimertinib and ramucirumab to treat lung cancer is not FDA approved and should be considered investigational.

About 234,000 new cases of lung and bronchus cancer were estimated for 2018 in the United States. In non-small cell lung cancer, the most common type of lung cancer, EGFR mutations are active in about 10-15 percent of patients of European descent and about 40 percent of patients of East Asian descent. The current approach to treating non-small cell lung cancer patients with the EGFR mutation is treatment with osimertinib.

In this study, researchers hope to determine whether adding ramucirumab to osimertinib is better at controlling NSCLC with EGFR mutations than osimertinib alone.

“We’re trying to add a drug called ramucirumab together with osimertinib,” said Xiuning Le, MD, PhD (pictured), sponsor-investigator of the study and a medical oncologist at MD Anderson. “So, in the experimental group, the patient will get two drugs rather than just one to see if the addition of ramucirumab will make the duration of response even longer.”

Participants in the study will be randomly assigned to one of two study groups, called arms. Participants on Arm A will receive osimertinib with ramucirumab, and participants on Arm B will receive osimertinib alone. Participants in both arms will continue study treatment until their disease gets worse or side effects become intolerable. Participants may discontinue treatment at any time in cooperation with their doctor.

“We’re trying to improve the inhibitors,” Dr. Le explained about osimertinib, a third-generation EGFR inhibitor. “It is very well tolerated and can induce a response in 80 to 90 percent of patients, and responses can last up to a year and a half to two years. However, MD Anderson and other groups have found that for patients who only get an EGFR inhibitor, the tumors outsmart the drug by making more VEGF to replace EGFR-functionally.”

By addressing both pathways, Dr. Le said, researchers hope they can treat the tumor for a longer period.

Up to 150 subjects may participate in the study. To qualify, participants must be adults 18 or older and have locally advanced or metastatic non-small cell lung cancer with EGFR mutation. Blood and tissue will be collected to support correlative research.

The study is supported by Eli Lilly and Company.

For more information about this research study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03909334).

About Hoosier Cancer Research Network 

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 230 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 9,000 subjects have participated in Hoosier Cancer Research Network clinical trials.