The FDA cleared Rozlytrek (entrectinib) for the treatment of adults with ROS1-positive, metastatic non-small-cell lung cancer, also granting accelerated approval to the tyrosine kinase inhibitor for adult and pediatric patients (12 and older) with solid tumors that have a NTRK gene fusion.

Approval in the U.S., granted to Basel, Switzerland-based Roche Holding AG's Genentech unit, comes about two months after Japan became the first country to give the go-ahead to Rozlytrek, which targets the kinase activity of TRK type A/B/C and ROS1 proteins. Their activating fusions drive proliferation in cancers such as breast, colorectal, gastric, head and neck, neuroendocrine, lung, ovarian, thyroid and pancreatic. (See BioWorld, June 24, 2019.)

The green-lighting of the Japan NDA, filed by Roche majority-owned subsidiary Chugai Pharmaceutical Co. Ltd., of Tokyo, was based primarily on the results from an open-label, global phase II study. Efficacy was evaluated in 51 adult patients with NTRK fusion gene-positive solid tumors, as well as in five pediatric patients, enrolled in overseas phase I and phase Ib studies.

Sandra Horning, Genentech's chief medical officer and head of global product development, noted that Rozlytrek is the first drug that hits ROS1 and NTRK fusions to win the FDA's nod, pointing out that the compound "has also shown responses in these rare cancer types that have spread to the brain."

In the U.S., Rozlytrek competes with Vitrakvi (larotrectinib), from Bayer AG, of Leverkusen, Germany, which won accelerated FDA approval in November as a treatment for adult and pediatric patients with NTRK fusion cancers. Vitrakvi was originally developed by Loxo Oncology Inc. in partnership with Bayer. Loxo was later acquired by Eli Lilly and Co., of Indianapolis. (See BioWorld, Jan. 8, 2019.)

Bayer in May teamed up with Roche's Foundation Medicine Inc. to develop genetic sequencing tests to identify patients who might benefit from various approved and investigational cancer therapies, and Vitrakvi was made the initial focus for a next-generation sequencing companion diagnostic. Vitrakvi as well as Rozlytrek are under review in Europe.