NICE issues Final Draft Guidance recommending that RYBREVANT®▼(amivantamab) with carboplatin and pemetrexed can be used during a managed access period for untreated advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) exon 20 insertion mutations in adults

High Wycombe, UK – Johnson & Johnson is pleased to announce today that the National Institute for Health and Care Excellence (NICE) has recommended that RYBREVANT®▼ (amivantamab) with carboplatin and pemetrexed can be used during a managed access period for untreated advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) exon 20 insertion mutations in adults, in its Final Draft Guidance.

This recommendation means that eligible patients in England and Wales may soon be treated with amivantamab in combination with carboplatin and pemetrexed on the National Health Service (NHS) via the Cancer Drugs Fund.

In England and Wales, more than 41,000 people were diagnosed with lung cancer in 2024. NSCLC is the most common type of lung cancer, accounting for 80-85 percent of all cases. Patients diagnosed with EGFR exon 20 insertion mutation-positive NSCLC are more likely to experience poorer prognoses and outcomes compared to other types of NSCLC with more common EGFR mutations, such as exon 19 deletions and exon 21 L858R substitution mutations. EGFR exon 20 insertion mutations are also more likely to occur in women, people from Asian ethnicities, and people with no history of smoking. There has long been a significant unmet need for targeted treatment options for this group of patients. EGFR exon 20 insertion mutated NSCLC is largely insensitive to tyrosine kinase inhibitors that have been approved for the treatment of patients with common EGFR-mutated NSCLC.

“This is a hugely important moment and marks a significant shift in care for people living with EGFR exon 20 insertion mutated non-small cell lung cancer, a group that has historically been overlooked and underserved,” said Prof. Virginia Harrison, Research Trustee, EGFR+ UK. “Too often, people with exon 20 insertion mutations have faced limited options compared to other EGFR subtypes, such as EGFR exon 19 deletions or exon 21 L858R substitution mutations. This decision has the potential to address that inequity and ensure patients finally have access to targeted therapies designed specifically for their disease.”

This milestone marks important progress in ensuring that eligible adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations are offered treatment pathways that reflect the underlying biology of their disease.

“This is a landmark moment for patients with EGFR exon 20 insertion-mutant lung cancer in the UK, a historically underserved group who have had limited access to targeted therapy. The NICE recommendation of amivantamab in combination with chemotherapy changes that entirely. We can now offer patients with this difficult-to-treat mutation a targeted treatment that addresses the biology driving their cancer, now available to NHS patients through the Cancer Drugs Fund. This recommendation will make a real difference to the lives of patients who have waited far too long,” said Dr Spyros Gennatas, Consultant Medical Oncologist, Guy’s and St Thomas’ NHS Foundation Trust.
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NICE’s recommendation is based on data from the Phase 3 PAPILLON study, which found that amivantamab with carboplatin and pemetrexed increased median progression-free survival (PFS) by blinded independent committee review (BICR) – the study’s primary endpoint – by 4.7 months (11.4 months versus 6.7 months) compared to carboplatin and pemetrexed alone.

In the dataset of amivantamab in combination with carboplatin and pemetrexed (N=301), the most frequent adverse reactions in all grades were rash (83 percent), neutropenia (57 percent), nail toxicity (53 percent), infusion related reactions (IRR) (51 percent), fatigue (43 percent), stomatitis (39 percent), nausea (43 percent), thrombocytopenia (40 percent), constipation (40 percent), oedema (40 percent), decreased appetite (33 percent), hypoalbuminaemia (32 percent), alanine aminotransferase increased (26 percent), aspartate aminotransferase increased (23 percent), vomiting (22 percent), and hypokalaemia (20 percent).6 Serious adverse reactions included rash (2.7 percent), venous thromboembolism (2.3 percent), thrombocytopenia (2.3 percent) and interstitial lung disease (ILD) (2.0 percent). Eight percent of patients discontinued amivantamab due to adverse reactions. The most frequent adverse reactions leading to treatment discontinuation were IRR (2.7 percent), rash (2.3 percent), ILD (2.3 percent), and nail toxicity (1.0 percent).

“We are delighted with NICE’s Final Draft Guidance which means that eligible patients in England and Wales with EGFR exon 20 insertion mutation-positive advanced NSCLC will soon have access through the Cancer Drugs Fund to a targeted therapy that addresses their specific type of cancer. The availability of this targeted treatment is crucial as we seek to make a real difference to these patients’ lives from day one,” said Amanda Cunnington, UK Senior Director of Patient Access, Johnson & Johnson Innovative Medicine. “We are committed to getting in front of cancer, and will work closely with partners across the healthcare system to ensure today’s positive announcement translates into timely and equitable uptake across the NHS. Thank you to everyone who contributed to the appraisal process.”