FDA Approves Rozlytrek for Breast Cancer, Other Solid Tumors with Specific Gene Defect

The U.S. Food and Drug Administration (FDA) has approved Rozlytrek (entrectinib) as an oral treatment for adult and adolescent patients whose breast cancer and other solid tumors have a specific genetic defect called NTRK gene fusion, have no other satisfactory therapy, is metastatic, or likely to experience severe complications are after surgical removal.

Rozlytrek also was approved by the FDA for adults with ROS1 mutation-positive, metastatic non-small cell lung cancer.

Both ROS1 and NTRK1/2/3 fusions with other genes can result in cancer cell proliferation. By blocking the enzymatic activity of the TRK A/B/C and ROS1 proteins, Genentech’s Rozlytrek may result in the death of tumor cells.

Rozlytrek’s effectiveness was evaluated in four clinical trials of 54 adults: the STARTRK-2 Phase 2 trial (NCT02568267), and the Phase 1 studies STARTRK-1 (NCT02097810), ALKA-372-001 and STARTRK-NG (NCT02650401). Both STARTRK-2 and STARTRK-NG trials are still enrolling participants; for more information, on their NCT identifiers.

The most common cancer locations were the breast, lung, salivary gland, thyroid, and colon/rectum. The results in NTRK fusion-positive tumors showed that 57% of the patients experienced substantial tumor shrinkage, with 7.4% having complete cancer disappearance. Among the 31 patients with tumor size reduction, 61% showed tumor shrinkage for at least nine months.

In a press release, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, noted that the approval for pediatric patients (12 and older) was based on efficacy data collected in adults, although the team analyzed Rozlytrek’s safety in 30 adolescents.

“Traditionally, clinical development of new cancer drugs in pediatric populations is not started until development is well underway in adults, and often not until after approval of an adult indication,” he said. “The FDA continues to encourage the inclusion of adolescents in clinical trials, said Pazdur, who also is acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

As for the studies in ROS1-positive lung cancer, 40 of the 51 (78%) adult patients showed tumor shrinkage, with 5.9% experiencing complete cancer disappearance. Most patients (55%) whose cancer responded to treatment had tumor shrinkage for 12 months or longer.

This is the third FDA approval of a cancer therapy based on biomarkers of different tumors rather than on the body location where the tumor originated. Such medications, which include Keytruda (pembrolizumab, by Merck) for tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and Vitrakvi (larotrectinib, by Bayer) also for tumors with NTKR gene fusions, are called “tissue agnostic.”

These approvals follow an FDA guidance document released in 2018.

“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,” said Ned Sharpless, MD, the FDA’s Acting Commissioner.

“Using the FDA’s expedited review pathways,” Sharpless said, “we’re supporting this innovation in precision oncology drug development and the evolution of more targeted and effective treatments for cancer patients. We remain committed to encouraging the advancement of more targeted innovations in oncology treatment and across disease types based on our growing understanding of the underlying biology of diseases.”

Detailed information on side effects associated with taking Rozlytrek can be found here.

The FDA granted accelerated approval to Rozlytrek, which means that Genentech is required to provide additional data.

The treatment was first approved in Japan in June for adults and pediatric patients with NTRK fusion-positive, advanced recurrent solid tumors.