Rare Daily Staff

The U.S. Food and Drug Administration approved Genentech’s Rozlytrek for the treatment of two rare cancers.

The agency approved Rozlytrek for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC). The agency also granted accelerated approval to Rozlytrek for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic, or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.

More than an estimated 228,000 Americans will be diagnosed with lung cancer in 2019, and NSCLC accounts for 84 percent of all lung cancers, according to the American Cancer Society. About 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages. While the ROS1 gene fusion can be found in any person with NSCLC, young people who have never smoked have the highest incidence of ROS1-positive NSCLC.

Neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in the proliferation of certain types of cancer. NTRK gene fusions are present in tumors irrespective of site of origin. NTRK gene fusions have been identified in a broad range of solid tumor types, with a higher incidence in certain tumor types including NSCLC.

Rozlytrek is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Rozlytrek can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions. Biomarker testing for ROS1 in NSCLC and NTRK gene fusions across all solid tumors is the only way to identify people who are eligible for treatment with Rozlytrek.

The approval of Rozlytrek was based on an integrated analysis including data from 51 people with ROS1-positive NSCLC and 54 people with locally advanced or metastatic NTRK gene fusion-positive solid tumors from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials. This approval is also based on data from the phase I/II STARTRK-NG study in pediatric patients. The studies enrolled people across 15 countries and more than 150 clinical trial sites.

Safety was assessed from an integrated analysis of 355 people across these four trials. The most common adverse reactions with Rozlytrek 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 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,” said Sandra Horning, chief medical officer and head of Global Product Development. “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.”

Photo: Sandra Horning, chief medical officer and head of Global Product Development

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