Roche's Rozlytrek Receives FDA Approval for Two Tumor-Agnostic Indications: NTRK Fusion-Positive Solid Tumors and ROS1-Positive NSCLC

On August 16, 2019, VCBeat (WeChat ID: vcbeat) learned from foreign media reports that Roche announced the FDA had approved its tissue-agnostic anticancer drug Rozlytrek (generic name: entrectinib) for the treatment of pediatric and adult patients aged 12 years and older with solid tumors harboring NTRK gene fusions. The agency also approved Rozlytrek for the treatment of adult patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC). There are currently no effective treatments for these conditions.

This is the third “tissue-agnostic” anticancer therapy approved by the FDA, following Keytruda and Vitrakvi. These therapies target specific genetic drivers of cancer rather than the tissue type from which the tumor originates. The approval was based on results from multiple clinical trials, including the pivotal Phase 2 STARTRK-2 trial and the Phase 1 trials STARTRK-1 and ALKA-372-001. Rozlytrek had previously received FDA Breakthrough Therapy designation and Accelerated Approval eligibility.

According to estimates by the American Cancer Society, more than 228,000 Americans will be diagnosed with lung cancer in 2019, with non-small cell lung cancer (NSCLC) accounting for 84% of all lung cancer cases. It is estimated that approximately 60% of lung cancer diagnoses in the United States are made at an advanced stage of the disease. Although ROS1 gene fusions can be found in any patient with non-small cell lung cancer, the highest incidence of ROS1-positive NSCLC occurs in young never-smokers. NTRK gene fusions have been identified across a wide range of solid tumor types, with a higher prevalence in certain tumor types, including non-small cell lung cancer (NSCLC).

The U.S. Food and Drug Administration stated that among patients with NTRK fusion-positive solid tumors, 57% exhibited significant tumor shrinkage, with 7.4% achieving complete tumor disappearance. Furthermore, among the 31 patients who experienced tumor shrinkage, 61% maintained this response for nine months or longer. For patients with ROS1-positive non-small cell lung cancer (NSCLC), the agency reported an overall response rate of 78%, with 5.9% of patients achieving complete cancer remission. Additionally, among the 40 patients whose tumors shrank, 55% sustained this reduction for at least 12 months.

NTRK fusion-positive tumors arise from fusions between NTRK1/2/3 genes and other genes, resulting in abnormal TRK proteins (TRKA/TRKB/TRKC) that activate signaling pathways associated with the proliferation of specific cancers. NTRK gene fusions may occur in tumors originating from various anatomical sites, including breast cancer, cholangiocarcinoma, colorectal cancer, neuroendocrine tumors, non-small cell lung cancer (NSCLC), and pancreatic cancer, among others.

Rozlytrek is a selective tyrosine kinase inhibitor designed to target NTRK and ROS1 gene fusions, capable of inhibiting the kinase activity of TRK A/B/C and ROS1. Developed by Ignyta, which was acquired by Roche for $1.7 billion in 2017, Rozlytrek received its initial approval in Japan this June for the treatment of patients with advanced, recurrent solid tumors harboring NTRK gene fusions.

Sandra Horning, Chief Medical Officer and Global Head of Product Development at Roche, commented: “The approval of Rozlytrek for two rare cancers represents a significant advance for patients; it is the first FDA-approved therapy selectively targeting ROS1 and NTRK fusions.”

“We are in an exciting era marked by a surge of innovative anticancer therapies. The development of ‘tumor-agnostic’ therapies has the potential to bring revolutionary changes to cancer treatment. Progress continues to be made in using biomarkers to guide drug development and targeted drug delivery,” said Dr. Ned Sharpless, Acting Commissioner of the FDA.

Roche, founded in 1896 and headquartered in Basel, Switzerland, is a global leader in oncology drug research and development. To date, Roche’s research laboratories worldwide have been associated with three Nobel Prizes. Historically, Roche’s business operations primarily spanned four sectors: pharmaceuticals, medical diagnostics, vitamins and fine chemicals, and fragrances and flavors. Additionally, Roche engages in the development, commercialization, and sales of products in key therapeutic areas, including neuroscience, virology, infectious diseases, oncology, cardiovascular diseases, inflammation and immunology, dermatology, metabolic disorders, and osteoarticular diseases.

(Compiled by Cheng Tao)