FDA Approves Rozlytrek

FDA Approves Rozlytrek (entrectinib) for People With ROS1-Positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumors

South San Francisco, CA -- August 15, 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 approved Rozlytrek (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.

These approvals 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/II STARTRK-NG study. In the integrated analysis, Rozlytrek was studied in several solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers. In ROS1-positive, metastatic NSCLC, Rozlytrek shrank tumors in 78% of people with the disease (overall response rate [ORR]; N=51) and the duration of response (DoR) ranged from 1.8 to 36.8+ months (N=40 out of 51). Rozlytrek also shrank tumors in more than half of people with NTRK gene fusion-positive, locally advanced or metastatic solid tumors (ORR=57%; N=54), and objective responses were observed across 10 tumor types (DoR ranged from 2.8 to 26.0+ months; N=31 out of 54). Objective responses to Rozlytrek were seen in people with central nervous system (CNS) metastases at baseline.

“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,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “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.”

“The identification of actionable biomarkers like ROS1 has brought about significant progress in the treatment of lung cancer. This approval brings further hope to people with this rare type of the disease,” said Janet Freeman-Daily, co-founder of The ROS1ders, a group of patients and caregivers affected by ROS1-positive lung cancer. “Up to 40% of people with ROS1-positive non-small cell lung cancer have tumors that have spread to the brain, so now there is a new treatment option for those patients.”

The most common adverse reactions (≥20 percent) with Rozlytrek were fatigue, constipation, altered sense of taste (dysgeusia), swelling (edema), dizziness, diarrhea, nausea, nervous system disorders (dysesthesia), shortness of breath (dyspnea), muscle pain (myalgia), cognitive impairment, increased weight, cough, vomiting, fever (pyrexia), joint pain (arthralgia) and vision disorders.

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious or life-threatening disease or condition. The accelerated approval of Rozlytrek 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.

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. Genentech is leveraging its expertise in developing personalized medicines and advanced diagnostics, in conjunction with Foundation Medicine, to help identify people with ROS1 and NTRK gene fusions. Foundation Medicine will submit Foundation®One CDx to the FDA for approval as a companion diagnostic for Rozlytrek. An FDA-approved companion diagnostic for Rozlytrek is not available at this time.

Rozlytrek is now available in the United States for adults and children 12 years of age and older. For those who qualify, Genentech offers patient assistance programs for people prescribed Rozlytrek by their doctor through Genentech Access Solutions. Please contact Genentech Access Solutions at (866) 422-2377 or visit http://www.Genentech-Access.comfor more information.

About the Integrated Analysis

This approval is based on an integrated analysis including data from 51 people with ROS1-positive NSCLC and 54 people with locally advanced or metastatic NTRK gene 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. This approval is also based on data from the Phase I/II STARTRK-NG study in pediatric patients. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Safety was assessed from an integrated analysis of 355 people across these four trials.

About Lung Cancer

According to the American Cancer Society, it is estimated that more than 228,000 Americans will be diagnosed with lung cancer in 2019, and NSCLC accounts for 84 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages. While the ROS1 gene fusion can be found in any person with NSCLC, young never-smokers have the highest incidence of ROS1-positive NSCLC. NTRK gene fusions have been identified in a broad range of solid tumor types, with a higher incidence in certain tumor types including NSCLC.

About NTRK Gene Fusion-Positive Cancer

Neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in the proliferation of certain types of cancer. NTRK gene fusions are present in tumors irrespective of site of origin. These fusions have been identified in a broad range of solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

About Rozlytrek

Rozlytrek (entrectinib) is an oral medicine for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC), as well as 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. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Rozlytrek can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.

Indication

Rozlytrek is a prescription medicine used to treat:

• Adults with non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by an abnormal ROS1 gene
• Adults and children 12 years and older with solid tumors (cancer) that:
  • are caused by certain abnormal NTRK genes and
  • have spread or if surgery to remove their cancer is likely to cause severe complications, and
  • there is no satisfactory alternative treatment option or the cancer grew or spread on other treatment

It is not known if Rozlytrek is safe and effective for use in children less than 12 years of age.

Rozlytrek was approved in NTRK gene fusion-positive solid tumors through a faster FDA review process based on the percentage of patients whose tumor size shrank or disappeared after treatment and how long that response lasted. There are ongoing studies to confirm benefit of Rozlytrek for this use.

Important Safety Information

Rozlytrek may cause serious side effects, including:

• Congestive heart failure. Rozlytrek may cause congestive heart failure or make the congestive heart failure that a patient already has worse. Patients should tell their healthcare provider right away if they 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 mood, or may affect how a patient thinks and cause confusion, hallucinations, and problems with concentration, attention, memory, and sleep. Patients should tell their healthcare provider right away if they have any of these symptoms.
• Bone fractures. Rozlytrek may increase the risk of bone fractures. Bone fractures may happen with or without a fall or other injury. Patients should tell their healthcare provider if they have pain, changes in movement, or bone abnormalities.
• Liver problems (hepatotoxicity). A healthcare provider will do blood tests to check a patient’s liver function during treatment with Rozlytrek. Patients should tell their healthcare provider right away if they develop symptoms of liver problems including: loss of appetite, nausea or vomiting, or pain on the upper right side of the stomach area. A healthcare provider may temporarily stop treatment, decrease the dose, or permanently stop Rozlytrek if a patient develops liver problems with Rozlytrek.
• Increased uric acid level in the blood (hyperuricemia). Rozlytrek may cause an excess of uric acid in the blood. A healthcare provider may do tests before and during a patient’s treatment with Rozlytrek to check the uric acid level in the blood. A healthcare provider may prescribe medications if a patient has high blood uric acid levels.
• Changes in the electrical activity of the heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life-threatening. A healthcare provider will do tests before and during treatment with Rozlytrek to check the electrical activity of the heart and body salts (electrolytes). Patients should tell their healthcare provider right away if they feel faint, lightheaded, dizzy, or feel their heart beating irregularly or fast while taking Rozlytrek. These may be symptoms related to QT prolongation.
• Vision problems. Rozlytrek may cause vision problems. Healthcare providers may stop Rozlytrek and refer to an eye specialist if a patient develops severe vision problems during treatment with Rozlytrek. Patients should tell their healthcare provider right away if they 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 the eyes

  • Before taking Rozlytrek, patients should tell their healthcare provider about all their medical conditions, including if they:

    • 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 an unborn baby. Patients should tell their healthcare provider right away if they become pregnant during treatment with Rozlytrek or think they may be pregnant.
      • If patients are able to become pregnant, their healthcare provider will do a pregnancy test before they 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 breast milk. Do not breastfeed during treatment with Rozlytrek and for 7 days after the final dose of Rozlytrek. Patients should talk to their healthcare provider about the best way to feed their baby during this time.

    Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, or herbal supplements.

    Certain other medicines may affect how Rozlytrek works causing side effects. Patients should know the medicines they take. Patients should keep a list of them to show to their healthcare provider and pharmacist when they get a new medicine.

    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
    • cough
    • vomiting
    • fever
    • joint pain
    • vision changes
       

    These are not all the possible side effects of Rozlytrek. For more information, patients should ask their healthcare provider or pharmacist.

    Patients should call their doctor for medical advice about side effects.