The National Institute for Health and Care Excellence (NICE) has today published a final appraisal document recommending sotorasib for use within the Cancer Drugs Fund as an option for treating KRAS G12C mutation-positive locally advanced or metastatic non-small-cell lung cancer in adults whose disease has progressed on, or who cannot tolerate, platinum-based chemotherapy or anti-PD-1/PD-L1 immunotherapy, in accordance with the managed access agreement. 

Amgen’s first-in-class drug, Sotorasib, was the first new medicine to receive a Conditional Marketing Authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) for use across England, Scotland and Wales under Project Orbis.

The treatment, an oral targeted therapy, will now be available to suitable patients in England via the Cancer Drugs Fund, addressing an unmet need in previously treated patients with KRAS G12C NSCLC, a mutation which was previously thought to be “undruggable”.

Lung cancer is the third most common cancer with an estimated 48,000 new cases diagnosed in the UK every year. NSCLC accounts for 85% of lung cancers and approximately 13% of these are thought to have the KRAS G12C mutation.

Sotorasib represents a new treatment option for suitable patients who have had biomarker testing and been identified with this mutation.

Professor Sanjay Popat, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust said: “Sotorasib is a step-change for these patients, allowing them to receive daily tablets rather than chemotherapy in the hospital.

I’m therefore delighted NICE has approved this drug for patients via the Cancer Drug Fund. Importantly, in parallel, the NHS is making excellent progress in 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 at Amgen UK and Ireland said: “Sotorasib provides a new treatment option for appropriate patients whose lung cancer is found to have the KRAS G12C mutation. More than half of NSCLC patients have advanced or metastatic disease at diagnosis and outcomes across the UK remain poor.

Amgen is proud of our collaboration with both NHS England and NICE to ensure people living with NSCLC who may benefit from sotorasib can access the medicine without delay.”

Paula Chadwick, Chief Executive of Roy Castle Lung Cancer Foundation said: “This recommendation demonstrates all the hard work that is happening to develop new treatment options for people with lung cancer. The pandemic has had a devastating effect on these patients, potentially denying many of them the chance of an earlier, and possibly life-saving diagnosis.

However, the advances in new treatments like sotorasib offer some hope by giving people another treatment option.” The NICE decision to recommend sotorasib for use in the Cancer Drugs Fund follows an agreement between Amgen and NHS England which has already enabled more than 100 patients to access the medicine following its Conditional Marketing Authorisation by MHRA via Project Orbis.

The Conditional Marketing Authorisation for sotorasib is based on clinical evidence from the Phase 2 CodeBreaK 100 study which evaluated the drug in 126 patients with KRAS G12Cmutated advanced NSCLC.

This trial demonstrated an Objective Response Rate ORR (primary endpoint) of 37.1% (95% confidence interval [CI], 28.6 to 46.2), and an Overall Survival OS (secondary endpoint) of 12.5 months (95% CI, 10.0 to not evaluable). Among 46 patients with ORR, the median Duration of Response (DoR) was 10.0 months (95% CI, 1.2 to 11.1). 

The most common adverse reactions observed with sotorasib were diarrhoea (34%), musculoskeletal pain (31%), nausea (25%), fatigue (21%), hepatotoxicity (19%) and cough (16%).

The most common severe (grade ≥ 3) adverse reactions were increased ALT (5%), increased AST (4%), and diarrhoea (4%). The most common adverse reactions leading to permanent discontinuation of treatment were increased ALT (1%), increased AST (1%) and drug-induced liver injury (1%).

The most common adverse reactions leading to dose modification were increased ALT (6%), increased AST (6%), and diarrhoea (6%).1

*This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This means that further evidence on this medicinal product is awaited.

Source: Amgen Oncology