Rozlytrek approved for ROS1-positive metastatic NSCLC, cancers with NTRK gene fusion defects


Rozlytrek (entrectinib) has been approved to treat cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusion defects in adults and adolescents for whom there are no effective treatments, the Food and Drug Administration announced in a press release.

A stamp saying "FDA approved." Olivier Le Moal/Getty Images

Entrectinib was also approved for the treatment of adults with metastatic non–small cell lung cancers that are ROS1-positive.

“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. We’re seeing continued advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine,” FDA Acting Commissioner Ned Sharpless, MD, said in the release.

This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than on the original tumor’s location. The previous tissue-agnostic indications approved by the FDA were pembrolizumab (Keytruda) for tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in 2017 and larotrectinib (Vitrakvi) for NTRK gene fusion tumors in 2018.

The approval of entrectinib was granted to Genentech. “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,” Sandra Horning, MD, chief medical officer and head of global product development for Genentech, said in a separate press release.

Foundation Medicine will submit Foundation One CDx to the FDA for approval as a companion diagnostic for entrectinib, according to the Genentech release; an FDA-approved companion diagnostic for entrectinib is not available at this time.

“Today’s approval includes an indication for pediatric patients, 12 years of age and older, who have NTRK fusion–positive tumors by relying on efficacy information obtained primarily in adults,” said Richard Pazdur, 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 Evaluation and Research. “Efficacy in adolescents was derived from adult data and safety was demonstrated in 30 pediatric patients.”

Entrectinib was evaluated in four clinical trials that included 54 adults with NTRK fusion–positive tumors. The overall response rate was 57%, with 7.4% of patients having complete disappearance of the tumor. Among the 31 patients with tumor shrinkage, 61% had tumor shrinkage persist for 9 months or longer. The most common cancer locations were the lung, salivary gland, breast, thyroid, and colon/rectum.

Clinical studies evaluated 51 adults with ROS1-positive lung cancer. The overall response rate was 78%, with 5.9% of patients having complete disappearance of their cancer. Among the 40 patients with tumor shrinkage, 55% had tumor shrinkage persist for 12 months or longer.

The most serious side effects of entrectinib are heart failure, central nervous system effects, changes in sleep pattern, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders. Females of reproductive age and males with a female partner of reproductive potential are advised to use effective contraception during treatment; the drug may cause harm to a developing fetus or newborn baby.

Genentech must provide additional clinical trial data to the FDA as a condition of the approval.

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