FDA Approves Genentech’s Personalized Medicine for Two Different Indications in ROS1-Positive Non-Small Cell Lung Cancer and NTRK Fusion-Positive Solid Tumors

August 15th, 2019

On August 15, 2019, the FDA approved Genentech’s RozlytrekTM (entrectinib) for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC). The FDA has 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. The accelerated approval for NTRK gene fusion-positive solid tumors is based on tumor response rate and durability of response, and continued approval may be contingent upon verification and description of clinical benefit in the confirmatory trials.

News in brief

  • Rozlytrek is the first FDA-approved treatment selected to target both NTRK and ROS1 fusions that has also shown response in cancer that has spread to the brain.
  • Rozlytrek is Genentech’s first FDA-approved tumor-agnostic medicine.
  • 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.

Supporting Information

Important Safety Information

What is the most important information I should know about ROZLYTREK?

ROZLYTREK may cause serious side effects, including:

  • Congestive heart failure. ROZLYTREK may cause congestive heart failure or make the congestive heart failure that you already have worse. Tell your healthcare provider right away if you have any of the following signs and symptoms of congestive heart failure:
    • persistent coughing or wheezing
    • trouble breathing when lying down
    • sudden weight gain
    • increasing shortness of breath
    • tiredness, weakness, or fatigue
    • swelling in ankles, feet, or legs
  • Central nervous system (CNS) effects. ROZLYTREK may cause dizziness, changes in your mood, or may affect how you think and cause confusion, hallucinations, and problems with concentration, attention, memory, and sleep. Tell your healthcare provider right away if you have any of these symptoms. 
  • Bone fractures. ROZLYTREK may increase your risk for bone fractures. Bone fractures may happen with or without a fall or other injury. Tell your healthcare provider if you have pain, changes in movement, or bone abnormalities.  
  • Liver problems (hepatotoxicity). Your healthcare provider will do blood tests to check your liver function during treatment with ROZLYTREK. Tell your healthcare provider right away if you develop symptoms of liver problems including: loss of appetite, nausea or vomiting, or pain on the upper right side of your stomach area. Your healthcare provider may temporarily stop treatment, decrease your dose, or permanently stop ROZLYTREK if you develop liver problems with ROZLYTREK.
  • Increased uric acid level in your blood (hyperuricemia). ROZLYTREKmay cause an excess of uric acid in your blood. Your healthcare provider may do tests before and during your treatment with ROZLYTREK to check the uric acid level in your blood. 
  • Changes in the electrical activity of your heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life-threatening. Your healthcare provider will do tests before and during your treatment with ROZLYTREK to check the electrical activity of your heart and your body salts (electrolytes). Tell your healthcare provider right away if you feel faint, lightheaded, dizzy, or feel your heart beating irregularly or fast during your treatment with ROZLYTREK. These may be symptoms related to QT prolongation.
  • Vision problems.ROZLYTREK may cause vision problems. Your healthcare provider may stop ROZLYTREK and refer you to an eye specialist if you develop severe vision problems during treatment with ROZLYTREK. Tell your healthcare provider right away if you have any loss of vision or any change in vision, including:
    • double vision
    • blurry vision
    • new or increased floaters
    • seeing flashes of light
    • light hurting your eyes

Before taking ROZLYTREK, tell your healthcare provider about all your medical conditions, including if you:

  • have liver or kidney problems.
  • have any heart problems, including a condition called long QT syndrome.
  • have nervous system (neurological) problems.
  • have or have had eye or vision problems. 
  • are pregnant or plan to become pregnant. ROZLYTREK can harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with ROZLYTREK or think you may be pregnant.
  • If you are able to become pregnant, your healthcare provider will do a pregnancy test before you start treatment with ROZLYTREK.
  • Females who are able to become pregnant should use effective birth control during treatment with ROZLYTREK and for at least 5 weeks after the final dose.
  • Males who have female partners that are able to become pregnant should use effective birth control during treatment with ROZLYTREK and for 3 months after the final dose.
  • are breastfeeding or plan to breastfeed. It is not known if ROZLYTREK passes into your breast milk. Do not breastfeed during treatment with ROZLYTREK and for 7 days after the final dose of ROZLYTREK. Talk to your healthcare provider about the best way to feed your baby during this time. 

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, or herbal supplements.

Certain other medicines may affect how ROZLYTREK works causing side effects. Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.  

What should I avoid while taking ROZLYTREK?

  • You should not drink grapefruit juice or eat grapefruit during your treatment with ROZLYTREK. It may increase the amount of entrectinib in your blood to a harmful level.
  • Do not drive or operate heavy machinery until you know how ROZLYTREK affects you. If you experience dizziness, fainting, tiredness, blurred vision, memory loss, changes in mental status, confusion, or hallucinations, do not drive or operate heavy machines until your symptoms resolve.

What are some possible side effects of ROZLYTREK?

The most common side effects of ROZLYTREK include:

  • tiredness
  • constipation
  • change in taste
  • swelling
  • dizziness
  • diarrhea
  • nausea
  • abnormal touch sensation
  • shortness of breath
  • muscle pain
  • confusion, mental status changes, memory problems, and hallucinations
  • weight gain
  • cough
  • vomiting
  • fever
  • joint pain
  • vision changes

These are not all the possible side effects of ROZLYTREK. Call your doctor for medical advice about side effects. 

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see additional Important Safety Information in full Prescribing Information, including Patient Information.

Sandra Horning, M.D.

"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. 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.”