Rozlytrek, Roche’s first tumour-agnostic therapy, approved in Switzerland for people with NTRK fusion-positive solid tumours and for people with ROS1 fusion-positive advanced non-small cell lung cancer

  • Rozlytrek has shown durable responses across multiple tumour types, including cancer that has spread to the brain
  • This approval shows the value of combining genomic profiling with precision medicine to offer patients with rare and hard-to-treat cancers a personalised treatment option

             
Basel, 15 December 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the Swiss agency for therapeutic products (Swissmedic) has approved Rozlytrek® (entrectinib) for the treatment of adult and paediatric people 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a metastatic disease or where surgical resection is likely to result in severe morbidity, and who have no known NTRK resistance Mutation, who have no satisfactory treatment options or that have progressed after prior therapy. Swissmedic has also approved Rozlytrek as monotherapy for the treatment of adults with ROS1 fusion-positive, advanced non-small cell lung cancer (NSCLC).1

“The approval of Entrectinib is a further step forward in personalised tumour treatment. Tumours with NTRK or ROS1 fusions are rare and patients have had relatively few treatment options to date. Immunotherapies are less effective for these tumours and chemotherapy is associated with side effects. Oral and well-tolerated drugs such as Entrectinib have many advantages for patients, which is why I also very much welcome the new approval”, said Prof. Dr. med. Oliver Gautschi, Co-chief Physician, Medical Oncology, Lucerne Cantonal Hospital.

“We are excited to announce the approval of Rozlytrek in Switzerland for patients with NTRK fusion-positive solid tumours and ROS1 fusion-positive NSCLC, that benefits patients even when their cancer has spread to the brain,” said Jean-Marc Häusler, M.D., Country Medical Director, Roche Pharma Switzerland. “This advance represents another important step forward in precision medicine by allowing us to treat certain cancer with NTRK gene fusions irrespective of the location of the tumour within the body.”

The approval is 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. These studies demonstrate that Rozlytrek has durable responses across several NTRK gene fusion-positive solid tumours, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma and gastrointestinal cancers, as well as ROS1-positive NSCLC.1

Results showed:
- Rozlytrek shrank tumours in more than half of patients with NTRK-fusion positive, locally advanced or metastatic solid tumours (overall response rate [ORR]=63.5% (95-%-KI 51.5, 74.4); N=74), and objective responses were observed across 13 tumour types1
- In patients with ROS1-fusion positive, advanced NSCLC, Rozlytrek shrank tumours in 73,4 % of patients with the disease (ORR; 95-%-KI 63.3, 82.0; N=94).1
- Objective responses to Rozlytrek were also seen in people with CNS metastases at baseline, with an intracranial ORR (IC-ORR) of 62.5% (95%-KI 24.5, 91.5; N=8) and 77,8 % (95-%-KI 52.36, 93.59; N=18), in both NTRK-fusion and ROS1-fusion positive populations, respectively.1
- The most common adverse reactions (≥20 percent) with Rozlytrek were fatigue, constipation, altered sense of taste (dysgeusia), swelling (oedema), dizziness, diarrhoea, nausea, paresthesia, shortness of breath (dyspnoea), anaemia, increased weight, increased blood creatinine, pain, cognitive disorders, vomiting, cough, and fever (pyrexia).1

NTRK gene fusions have been identified in a range of solid tumour types, and are present in up to 90% of some rare cancer types and less than 1% of other more common tumours, including lung and colorectal.2

ROS1 gene fusions account for 1-2% of NSCLC, the most common type of lung cancer that accounts for up to 85% of all diagnoses.3,4

Comprehensive molecular diagnostics and biomarker testing for gene fusions of NTRK and ROS1 is the most effective way to identify patients whose tumours are driven by these fusion- oncogenes and are most eligible for treatment with Rozlytrek. Roche is leveraging its expertise in developing personalised medicines and advanced diagnostics, to develop a companion diagnostic that will help identify people with NTRK and ROS1 gene fusions.

About the integrated analysis
The approval in Switzerland is based on an integrated analysis including data from 74 patients with locally advanced or metastatic NTRK fusion-positive solid tumours (13 tumour types) and 94 patients with ROS1-fusion positive NSCLC from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials.1 It is also based on data from the phase I/II STARTRK-NG study in paediatric patients. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Safety was assessed from an integrated analysis of 504 people across these four trials.1

About NTRK fusion-positive cancer
NTRK-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 signalling pathways involved in the proliferation of certain types of cancer.5 Blocking this abnormal signalling can cause tumour cells to shrink or die.2,5

NTRK gene fusions are present in tumours irrespective of site of origin (tumour agnostic). These fusions have been identified in a broad range of solid tumour types, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma.1,2

About ROS1-positive NSCLC
ROS1 is a tyrosine kinase, which plays a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, cancer cells grow and proliferate in an uncontrolled manner. Blocking this abnormal signalling can cause tumour cells to shrink or die.3

ROS1 gene fusions account for 1-2% of NSCLC.3 Lung cancer is the leading cause of cancer-related death across the world.6 Each year, more than one and a half million people die as a result of the disease globally, equating to more than 4,000 deaths every day.6 NSCLC is the most common type of lung cancer and accounts for up to 85% of all lung cancer diagnoses.4 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 gene fusions.3

About Rozlytrek
Rozlytrek® (entrectinib) is a tumour-agnostic once-daily oral medicine for the treatment of metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRKA/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.7,8 Rozlytrek can block NTRK and ROS1 kinase activity and may result in the death of cancer cells with NTRK or ROS1 gene fusions.7,8

Rozlytrek was granted accelerated approval in August 2019 by the US Food and Drug Administration (FDA). In June 2019, Japan’s Ministry of Health, Labour and Welfare (MHLW) also approved Rozlytrek for the treatment of adult and paediatric patients with NTRK fusion-positive, advanced recurrent solid tumours, and later approved Rozlytrek in ROS1-positive NSCLC in February 2020. Rozlytrek has also received approvals by health authorities in Australia, Canada, Hong Kong, Israel, New Zealand, South Korea, Taiwan and Europe.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the twelfth consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
[1] Professional Information Rozlytrek®, www.swissmedicinfo.ch
[2] Cocco, E, et al. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018; 15:731–747
[3] Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012; 30(8):863-70.
[4] American Cancer Society. What is Non-small Cell Lung Cancer? [Internet; cited 2020 July 8]. Available from: https://www.cancer.org/cancer/lung-cancer/about/what-is.html
[5] Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023.
[6] GLOBOCAN. Lung Cancer. [Internet; cited 2020 July 8]. Available from: http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
[7] Ahn M-J, Cho BC, Siena S, et al. Entrectinib in patients with locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC). Presented at: IASLC 18th World Conference on Lung Cancer; October 15-18, 2017; Yokohama, Japan. Abstract 8564.
[8] Rolfo C, et al. Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500.

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