The FDA ( U.S. Food and Drug Administration ) has granted accelerated approval to Rozlytrek ( Entrectinib ), a treatment for adult and adolescent patients whose cancers have the specific genetic defect, NTRK ( neurotrophic tyrosine receptor kinase ) gene fusion and for whom there are no effective treatments.
This is the third time the Agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than the location in the body where the tumor originated.
The approval marks a new paradigm in the development of cancer drugs that are tissue agnostic. It follows the policies that the FDA developed in a guidance document released in 2018.
The previous tissue agnostic indications approved by the FDA were Pembrolizumab for tumors with microsatellite instability-high ( MSI-H ) or mismatch repair deficient ( dMMR ) tumors in 2017 and Larotrectinib for NTRK gene fusion tumors in 2018.
Rozlytrek'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.
The ability of Rozlytrek to shrink tumors was evaluated in four clinical trials studying 54 adults with NTRK fusion-positive tumors.
The proportion of patients with substantial tumor shrinkage ( 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 nine months or longer.
The most common cancer locations were the lung, salivary gland, breast, thyroid and colon / rectum.
Rozlytrek was also approved for the treatment of adults with non-small cell lung cancer whose tumors are ROS1-positive ( mutation of the ROS1 gene ) and has spread to other parts of the body ( metastatic ).
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.
Rozlytrek’s common side effects are fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, fever, arthralgia and vision disorders ( blurred vision, sensitivity to light, double vision, worsening of vision, cataracts, or floaters ).
The most serious side effects of Rozlytrek are congestive heart failure, central nervous system effects ( cognitive impairment, anxiety, depression including suicidal thinking, dizziness or loss of balance, and change in sleep pattern, including insomnia and excessive sleepiness ), skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation and vision disorders.
Health care professionals should inform females of reproductive age and males with a female partner of reproductive potential to use effective contraception during treatment with Rozlytrek. Women who are pregnant or breastfeeding should not take Rozlytrek because it may cause harm to a developing fetus or newborn baby.
Rozlytrek was granted accelerated approval. This approval commits the sponsor to provide additional data to the FDA.
Rozlytrek has also received Priority Review, Breakthrough Therapy and Orphan Drug designation. ( Xagena )
Source: FDA, 2019