Sotorasib Is Indicated As Monotherapy For The Treatment Of Adult Patients With KRAS G12C-Mutated Locally Advanced Or Metastatic Non-Small Cell Lung Cancer (NSCLC), Who Have Progressed On, Or Are Intolerant To, Platinum-Based Chemotherapy And/Or Anti PD-1/PD-L1 Immunotherapy1,5
Sotorasib Becomes The First New Cancer Medicine To Receive Conditional Marketing Authorisation In Great Britain Under The Project Orbis Review Framework; Phase 2 Clinical Trial Results Demonstrated 37.1% Of Patients Responded To Treatment With 80.6% Achieving Disease Control2
CAMBRIDGE, UK -- (10 September 2021) -- Amgen UK today announces that its first-in-class medicine sotorasib (a targeted KRAS G12C inhibitor formerly named AMG 510) has become the first new cancer therapy to receive Conditional Marketing Authorisation for use1 across England, Scotland and Wales by the Medicines and Healthcare products Regulatory Agency (MHRA) under Project Orbis. This authorisation follows a review of sotorasib’s role in treating patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with the KRAS G12C gene mutation.
KRAS is one of the most frequently mutated genes in human cancers.3 KRAS G12C is one of the most common identified or known driver mutations in NSCLC.4,9 Sotorasib, which is administered orally as a tablet formulation5, binds with a mutated KRAS G12C protein to ‘switch off’ the signals it sends to trigger cell division and cancer cell growth.3 Sotorasib has been shown to irreversibly bind to the inactive KRAS G12C protein, permanently locking it in an inactive state, leading to inhibition of cancer cell growth.3, 6-8
Project Orbis is an international collaborative programme between the U.S. Food and Drug Administration (FDA) and regulatory agencies worldwide. It is designed to deliver efficient and effective review of new oncology products and their potential benefit to patients and health systems. Project Orbis helps support earlier access to innovative new medicines, like sotorasib.
Professor Sanjay Popat, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said: “Lung cancer driven by the KRAS G12C mutation is a highly aggressive cancer when it has relapsed after standard treatments and sotorasib is a first-in-class medicine, allowing eligible patients to receive daily tablets rather than chemotherapy in the hospital. I’m therefore delighted to see this rapid MHRA Conditional Marketing Authorisation. Importantly, in parallel the NHS is making excellent progress in the molecular analysis of lung cancer patients to find the KRAS G12C mutation and identify those patients who are most likely to benefit from this treatment.”
Dr. Tony Patrikios, Executive Medical Director, Amgen UK and Ireland, said: “Today’s Conditional Marketing Authorisation by the MHRA marks an important moment in treating lung cancer patients, with a new targeted therapy, who have failed first-line treatment and face extremely poor outcomes with limited further treatment options. This reflects the clinical investigation programme, demonstrating the use of sotorasib in adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have progressed on, or are intolerant to, platinum-based chemotherapy and/or anti PD-1/PD-L1 immunotherapy.”5
“Sotorasib is the first targeted KRAS G12C inhibitor to be authorised for use in Great Britain. Targeting KRAS has been a 40-year quest by scientists and researchers around the World. Approximately 13% of patients with NSCLC harbour the KRAS G12C mutation3, 10 and whilst approximately 48,000 people are diagnosed with lung cancer every year in the UK12,13 it is estimated that 5,000 of these people will have KRAS G12C-mutated NSCLC.”
The MHRA review of sotorasib centred around the Phase 2 CodeBreaK 100 clinical study which evaluated sotorasib in 126 patients with KRAS G12C-mutated advanced NSCLC. Patients were treated with sotorasib 960 mg once daily orally, and prior to the trial, patients had progressed on platinum-based chemotherapy and/or PD1/PD-LI immunotherapy.2
Data presented earlier this year during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (held 28th – 31st January 2021), demonstrated for the major efficacy outcome measures, a confirmed objective response rate (ORR) of 37.1% (95% CI: 28.6, 46.2), and a disease control rate (DCR) of 80.6% (95% CI: 72.6, 87.2). Additional outcome measures included a median progression-free survival of 6.8 months (95% CI: 5.1, 8.2) (data cut-off of December 1, 2020).11
Recently published data in the New England Journal of Medicine show a median overall survival (OS) of 12.5 months (95% CI, 10.0 to could not be evaluated) among 124 evaluable patients, (data cut-off of March 15, 2021).2 The median duration of response (DoR), which was evaluated in 46 patients was shown to be 11.1 months (95% CI, 6.9 to could not be evaluated). (OS and DoR were secondary outcome measures).2
The most common adverse reactions were diarrhoea (34%), musculoskeletal pain (31%), nausea (25%), fatigue (21%), hepatoxicity (19%) and cough (16%).5 The most common severe (grade ≥3) adverse reactions were increased ALT (5%), increased AST (4%), and diarrhoea (4%).5 The most common adverse reactions leading to permanent discontinuation of treatment were increased ALT (1%), increased AST (1%) and drug-induced liver injury (1%).5 The most common adverse reactions leading to dose modification were increased ALT (6%), increased AST (6%), and diarrhoea (6%).5
NSCLC accounts for 80-85% of all lung cancers, and most patients (66%) are diagnosed with advanced or metastatic disease.12, 13 KRAS G12C is one of the most common identified or known driver mutations in NSCLC.4 There is a high unmet need for patients with advanced NSCLC receiving second or subsequent lines of therapy.2
Cancer Research UK estimates there are around 48,000 new lung cancer cases in the UK every year, making it the country’s third most common form of cancer.13 While rates of detected lung cancer have dropped considerably in the last 30 years, it remains a condition with a high mortality rate, accounting for 21% of all cancer deaths in the UK (data from 2018).12 People in the UK diagnosed with lung cancer have a one-year survival rate of 41% (data from 2013-2017) and a 5-year survival rate of 16% (data from 2013-2017).12 Only 9.5% of people diagnosed with lung cancer are predicted to survive their disease for 10 years of more.1
*Additional efficacy and safety data are being collected
Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, a KRAS G12C inhibitor. 6 Sotorasib was the first KRAS G12C inhibitor to enter the clinic and is being studied in 10 combinations with global sites spanning four continents.14 In just under three years, the CodeBreaK clinical development programme for sotorasib has established a clinical data set with more than 800 patients studied across 13 tumour types to date.15
Further information about sotorasib can be found in the Summary of Product Characteristics sent with this news release.
The CodeBreaK clinical development programme is designed to study the risk benefit associated with Amgen’s investigational drug sotorasib for patients with an advanced solid tumour with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.16,17
CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicentre study, enrolled patients with KRAS G12C-mutant solid tumours.16 Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumour type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate.16 The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST 1.1 at baseline.2, 11
A global Phase 3 randomised active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) includes sites across the UK.17
About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that aim to advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient's life – not just their cancer journey – so they can take control of their lives.
For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company's history, moving with great speed to advance those innovations for the patients who need them.
At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the centre of everything we do.
About Amgen in the UK and Ireland
Amgen is committed to the relentless pursuit of breakthroughs and making a sustainable contribution to healthcare. A biotechnology pioneer since 1980, Amgen serves patients by transforming the promise of science and biotechnology into therapies that have the power to restore health or save lives.
Amgen develops innovative medicines in cancer and long-term conditions by using advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. As one of the most forward-thinking and innovative biotech companies, Amgen’s growing portfolio of medicines tackle some of the biggest healthcare burdens facing society today.
The Amgen community in the UK and Ireland is one of Amgen’s largest outside of the company headquarters in California and is a European hub for research and development. More than 500 people at Amgen in the UK and Ireland contribute to the journey that turns molecules into medicines.
For more information, visit www.amgen.co.uk
Job code: UKI-510-0621-00005
Date of Preparation: September 2021
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