FDA Approves First Oncology Drug Targeting Both ROS1, NTRK Gene Fusions

Officials with the FDA have granted approval to entrectinib (Rozlytrek, Genentech) for 2 different cancer indications.

Officials with the FDA have granted approval to entrectinib (Rozlytrek, Genentech) for 2 different indications in ROS1-positive non-small cell lung cancer (NSCLC) and neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumors, according to a press release.

In the NSCLC indication, entrectinib can be used for the treatment of adults with ROS1-positive, metastatic disease. The other indication, which received accelerated approval, is for the treatment of adults and adolescents whose cancers have the specific genetic defect NTRK gene fusion.

Entrectinib represents a tumor-agnostic approach to cancer treatment, meaning that the drug is designed to target a specific genetic driver of cancer regardless of a tumor's site of origin. According to the FDA, this is the third oncology drug to be approved based on a common biomarker across different types of tumors rather than location of tumor origin. Eligibility is determined by biomarker testing for ROS1 in NSCLC and NTRK gene fusions across all solid tumors.

Entrectinib’s approval for NTRK fusion-positive tumors was based on 4 clinical trials evaluating 54 adults. Overall, the data showed that the proportion of patients with substantial tumor shrinkage was 57%, with 7.4% of patients having complete disappearance of the tumor. Of the 31 patients with tumor shrinkage, 61% had tumor shrinkage persist for 9 months or longer, according to the study. The most common cancer locations were the lung, salivary gland, breast, thyroid, and colon/rectum.

Entrectinib’s approval for use in pediatric patients 12 years of age and older for this indication is based on efficacy information obtained primarily in adults, according to Richard Pazur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the office of Hematology and Oncology Products in the FDA’s Center for Drug and Evaluation Research.

“Traditionally, clinical development of new cancer drugs in pediatric populations is not started until development is well underway in adults, and often not until after approval of an adult indication,” Dr Pazur said in a statement. “Efficacy in adolescents was derived from adult data and safety was demonstrated in 30 pediatric patients.”

Additionally, entrectinib’s NSCLC indication was based on clinical studies including 51 patients. The results showed that the overall response rate was 78%, with 5.9% of patients having complete disappearance of their cancer. Of the 40 patients with tumor shrinkage, 55% had tumor shrinkage persist for 12 months or longer.

The most common adverse events seen with entrectinib were fatigue, constipation, altered sense of taste, swelling, dizziness, diarrhea, nausea, nervous system disorders, shortness of breath, muscle pain, cognitive impairment, increased weight, cough, vomiting, fever, joint pain, and vision disorders.

“Rozlytrek’s FDA approval for 2 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, said. “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.”


FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor [news release]. FDA.https://www.fda.gov/news-events/press-announcements/fda-approves-third-oncology-drug-targets-key-genetic-driver-cancer-rather-specific-type-tumor. Accessed August 15, 2019.

FDA Approves Genentech's Rozlytrek (entrectinib) for People With ROS1-Positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumors [news release]. Genentech. https://www.gene.com/media/press-releases/14802/2019-08-15/fda-approves-genentechs-rozlytrek-entrec. Accessed August 15, 2019.

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