HomeFDA Grants Priority Review to Entrectinib

FDA Grants Priority Review to Entrectinib

South San Francisco, CA, 18.02.2019

"Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Applications (NDAs) andgranted Priority Review for entrectinib for the treatment of adult and pediatric patients with neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive, locally advanced or metastatic solid tumors who have either progressed following prior therapies or as initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic, ROS1-positive non-small cell lung cancer (NSCLC). These NDAs are based on results from the integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the Phase I/Ib STARTRK-NG study. The FDA is expected to make a decision on approval by August 18, 2019.

“Entrectinib represents a unique approach to cancer treatment that can potentially target a range of hard-to-treat and rare NTRK fusion-positive tumors regardless of their site of origin, as well as treat ROS1-positive non-small cell lung cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “By combining comprehensive genomic profiling with actionable targeted therapies, like entrectinib, we are advancing our personalized healthcare goal to find the right treatment for each patient. We are working closely with the FDA to make this potential new option available as soon as possible."

The FDA grants Priority Review to medicines determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a serious disease. Entrectinib was also granted Breakthrough Therapy Designation (BTD) by the FDA in May 2017 for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies. BTD is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible.

Genentech is leveraging its expertise in developing personalized medicines and advanced diagnostics, in conjunction with Foundation Medicine, to develop a companion diagnostic that will help identify people with ROS1 and NTRK gene fusions.

About the integrated analysis

The integrated analysis included data from 53 people with ROS1-activating gene fusions and 54 people with locally advanced or metastatic NTRK fusion-positive solid tumors (10 tumor types, >19 histopathologies) from the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials. In addition, data from the Phase I/Ib STARTRK-NG study in pediatric patients were also included in the NDAs. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Tumor types evaluated in the studies to date included breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

  • STARTRK-2 is a Phase II, global, multicenter, open-label basket study in people with solid tumors that harbor an NTRK1/2/3, ROS1 or ALK-positive gene fusion. The primary endpoint is objective response rate (ORR), and duration of response (DoR) is a secondary endpoint. Other secondary outcome measures include time to response, clinical benefit rate, intracranial tumor response, progression-free survival (PFS), central nervous system (CNS) PFS and overall survival (OS).
  • STARTRK-1 is a Phase I, multicenter, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumors with NTRK1/2/3, ROS1 or ALK gene fusions in the U.S. and South Korea. The trial assessed the safety and tolerability of entrectinib via a standard dose escalation scheme and determined the recommended Phase II dose.
  • ALKA-372-001 is a Phase I, multicenter, open-label dose escalation study of an intermittent and continuous entrectinib dosing schedule in people with advanced or metastatic solid tumors with TRKA/B/C, ROS1 or ALK gene fusions in Italy.
  • STARTRK-NG is a Phase I/Ib dose escalation and expansion study evaluating the safety and efficacy of entrectinib in children and adolescent patients with no curative first-line treatment option, recurrent or refractory extracranial solid tumors or primary CNS tumors, with or without TRK, ROS1 or ALK fusions.

Results from the integrated analysis showed entrectinib shrank tumors (ORR) in more than half (57.4 percent) of people with NTRK fusion-positive solid tumors. Objective responses to entrectinib were seen across 10 different solid tumor types (median DoR = 10.4 months), including in people with and without CNS metastases at baseline. In these studies, entrectinib shrank tumors that had spread to the brain in more than half of people (intracranial response [IC ORR] = 54.5 percent), with more than a quarter of these people having a complete response.

Entrectinib shrank tumors in 77.4 percent of people with locally advanced or metastatic ROS1-positive NSCLC. In addition, entrectinib demonstrated a durable response of more than two years (median DoR = 24.6 months). Importantly, entrectinib was shown to shrink intracranial tumors in more than half of people with CNS metastases at baseline (IC ORR = 55.0 percent).

The safety profile of entrectinib was consistent with that seen in previous analyses. The most commonly reported adverse reactions included fatigue, constipation, altered sense of taste (dysgeusia), swelling (edema), dizziness, diarrhea, nausea, nervous system disorders (dysesthesia), shortness of breath (dyspnea), pain, anemia, cognitive disorders, weight increased, vomiting, cough, blood creatinine increase, joint pain (arthralgia), fever (pyrexia), and muscle pain (myalgia)."

 

More info on Genentech website.