LATE-BREAKING research on the use of amivantamab as a treatment for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) exon 20 insertion mutations following failure of platinum-based therapy has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP). This treatment will be the first of its kind used in the European Union (EU) for the specific targeting of EGFR exon 20 insertion mutations in advanced forms of the disease. This research comes from the CHRYSALIS study, and was presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program, with updated results presented at the IASLC World Conference on Lung Cancer (WCLC) 2020.
NSCLC is a prevalent form of lung cancer, with EGFR mutations present in 16–19% of Caucasian patients, and 37–41% of Asian patients. Patients with the specific EGFR exon 20 insertion mutation currently have a poor prognosis, with real-world five-year overall survival rate <8%. Existing treatments do not target this specific mutation, and the response observed to these treatments is often poor. Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), JanssenCilag AG, explained: “The decision today by the CHMP recognises amivantamab has the potential to provide an urgently required, effective, and tolerable new treatment option specifically targeted for patients diagnosed with non-small cell lung cancer who have EGFR exon 20 insertion mutations.”
Amivantamab, a fully human EGFR and MET bispecific antibody, targets tumours with activating and resistant EGFR and MET mutations and amplifications through its immune cell-directing activity. The Phase I CHRYSALIS study evaluated amivantamab as a monotherapy in patients following treatment with platinum-based therapy. This multicentre, open-label clinical study saw complete or partial responses in 32 out of 81 patients involved, and an overall response rate of 40%. A median progression-free survival of 8.3 months was also noted, as well as a median overall survival rate of 22.8 months. Peter Lebowitz, Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC, noted: “Amivantamab has the potential to address the high unmet need in the treatment of people with EGFR exon 20 insertion mutations in non-small cell lung cancer.” The European marketing authorisation application for amivantamab was based on these results.
Although some adverse events were noted, these were mainly reactions related to infusion, and were classed Grade 1-2. Ninety-four percent of these reactions occurred during the first infusion and did not impact treatment continuation in most cases. Some adverse reactions resulted in treatment discontinuation and dose reductions, in 4 and 13% of patients, respectively, and no treatment-related deaths occurred.
Amivantamab was approved by the U.S. Food and Drug Administration (FDA) in May 2021 for the treatment of adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed following platinum-based chemotherapy. The drug is expected to be authorised by the European Commission later this year. Lebowitz concluded: “we are committed to delivering innovative therapies and making a meaningful impact in areas of high unmet need and in the lives of patients. With the development of a novel bispecific antibody like amivantamab, we believe advancing medicines targeting specific pathways can bring the greatest benefits and improve outcomes for patients with tumour alterations such as EGFR and MET.”