AMGEN KRAS G12C INHIBITOR LUMYKRAS™▼ (SOTORASIB) RECEIVES CONDITIONAL MARKETING AUTHORISATION* BY MHRA FOR USE IN GREAT BRITAIN

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 mutation^{3, 10} and whilst approximately 48,000 people are diagnosed with lung cancer every year in the UK^12,13 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 28^th – 31^st 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.¹²

References

1. Amgen internal information.
2. Skoulidis F, et al. New England Journal of Medicine. 2021. 384:2371-2381 DOI: 10.1056/NEJMoa2103695.
3. Cox AD, et al. Nat Rev Drug Discov. 2014;13:828–51.
4. Liu P, et al. Acta Pharmaceutica Sinica B. 2019;9:871–879.
5. Amgen. LUMYKRAS™ Summary of Product Characteristics.
6. Canon J, et al. Nature. 2019;575:217-223.
7. Ryan MB, et al. Nat Rev Clin Oncol. 2018;15:709-720.
8. Simanshu DK, et al. Cell. 2017;170:17-33.
9. Román M, et al. Molecular Cancer (2018) 17:33: 2-14.
10. Biernacka A, et al. Cancer Genet. 2016;209:195-198.
11. Li BT, et al. Presentation at 2020 World Congress on Lung Cancer Singapore Worldwide Virtual Event, January 28-31, 2021. Abstract PS01.07.
12. Cancer Research UK. Cancer Statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-Two. Accessed August 2021.
13. Cancer Research UK. Types of Lung Cancer. Available at: https://www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types-grades/types. Accessed August 2021.
14. ClinicalTrials.gov. Available at: https://clinicaltrials.gov. Accessed August 2021.
15. Amgen Data on File.
16. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03600883. Accessed August 2021.
17. ClinicalTrials.gov. Available at: https://www.clinicaltrials.gov/ct2/show/NCT04303780. Accessed August 2021.https://clinicaltrials.gov/ct2/show/NCT03600883. Accessed August 2021https://clinicaltrials.gov/ct2/show/NCT03600883. Accessed August 2021

Job code: UKI-510-0621-00005

Date of Preparation: September 2021