FDA Approves Entrectinib for NTRK Fusion-Positive Solid Tumors and Rare Lung Cancer

FDA has granted accelerated approval to Genentech’s entrectinib, sold as Rozlytrek, for the treatment of adult and adolescent patients with solid tumors with that have the neurotrophic tyrosine receptor kinase (NTRK) gene fusion and for whom there are no effective treatments.

The approval of the tissue agnostic therapy represents a new paradigm in cancer treatment where cancers are treated based on a common biomarker seen across different tumors rather than based on the location in the body where the tumor originated. Last year, the FDA approved larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with advanced solid tumors expressing NTRK, and in 2017, pembrolizumab was approved for tumors with microsatellite instability-high or mismatch repair deficient tumors.

“We are in an exciting era of innovation in cancer treatment as we continue to see development in tissue agnostic therapies, which have the potential to transform cancer treatment,” FDA Acting Commissioner Ned Sharpless, MD, said in a statement. “We’re seeing continued advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine.”

Four clinical trials brought promising data for entrictinib and its ability to shrink NTRK fusion-positive tumors. Across the trials, there was an overall response rate (ORR) of 57%, with 7.4% of patients achieving a complete response (CR). There were 31 patients who had tumor shrinkage, 61% of which had responses that lasted 9 months or longer. The most common cancer locations were in the lung, salivary gland, breast, thyroid, and colon/rectum.

The FDA also gave approval to entrectinib for the treatment of adults with metastatic non—small cell lung cancer whose tumors are ROS1 positive. Trials assessing the drug in this setting showed that the entrictinib produced an ORR of 78% of 51 adults with ROS1-postive disease, of which 5.9% experienced a CR. Of the 40 patients who achieved a response, 55% had responses that lasted 12 months or longer.

“Rozlytrek’s FDA approval for two rare types of cancer is an important advance for patients, combining a targeted medicine and genomic testing to bring this new treatment option to patients who are waiting,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech, said in a statement. “Rozlytrek is the first FDA-approved treatment that selectively targets both ROS1 and NTRK fusions, and, importantly, has also shown responses in these rare cancer types that have spread to the brain.”

Common side effects of the treatment include fatigue, constipation, dysgeusia, edema, dizziness, cognitive impairment, weight gain, cough fever, and vision disorders. The most serious side effects include congestive heart failure, central nervous system effects, skeletal fractures, liver damage, and abnormal heart rhythm.