Janssen-Cilag International NV, a Johnson & Johnson company, has announced that the European Commission (EC) has approved a Type II variation for RYBREVANT (amivantamab) in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
“Patients with NSCLC harbouring EGFR exon 20 insertion driver mutations have high unmet needs and urgently require innovative treatment options to tackle the significant disease burden and poor prognosis they may face,” said trial investigator Professor Nicolas Girard, Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine at the Paris Saclay University, France. “Treatment with amivantamab has already been established in the second-line setting and with this approval in the first-line setting, amivantamab combined with chemotherapy has the potential to redefine the standard of care, offering improved patient outcomes both in terms of clinical efficacy and quality of life.”
EGFR exon 20 insertion mutations are the third most common activating EGFR mutation and are associated with real-world five-year overall survival rates as low as eight percent, making the introduction of new targeted therapeutic approaches tailored to address the unique complexities of EGFR exon 20 insertion mutations critical.
“At Johnson & Johnson, we are dedicated to advancing more effective and personalised innovations targeting novel disease pathways, that enable patients diagnosed with lung cancer to receive the treatment that is optimised for their individual characteristics,” said Henar Hevia, Ph.D, Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “Today’s approval is an important development for patients with EGFR exon 20 insertion-mutated non-small-cell lung cancer, who may now benefit from amivantamab plus chemotherapy at the start of their treatment journey.”
The expanded indication for amivantamab is based on positive results from the Phase 3 PAPILLON study, comparing the efficacy and safety of amivantamab in combination with chemotherapy (n=153) to chemotherapy alone (n=155) in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Data from the study were previously published in The New England Journal of Medicine.
The PAPILLON study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS; as measured by blinded independent central review [BICR]) in patients receiving amivantamab in combination with chemotherapy versus chemotherapy alone (hazard ratio [HR]=0.395; 95 percent confidence interval [CI], 0.30–0.53; P<0.0001). An interim overall survival (OS) analysis showed a favourable trend for patients treated with amivantamab plus chemotherapy, compared to those treated with chemotherapy alone (HR=0.675; 95 percent CI, 0.42–1.09; P=0.106).
The combination of amivantamab and chemotherapy demonstrated a safety profile consistent with the safety profiles of the individual agents, with low rates of treatment-related discontinuation with amivantamab (7 percent). The rates of overall adverse events (AEs) and AEs leading to death were comparable between both treatment arms. The rate of Grade ≥3 AEs was higher with amivantamab and chemotherapy, compared to chemotherapy alone (75 percent vs. 54 percent). Serious AEs (SAEs) occurred in 37 percent of patients with amivantamab and chemotherapy, compared to 31 percent with chemotherapy alone. EGFR and MET-related AEs were increased with amivantamab-chemotherapy (primarily Grade 1-2). Chemotherapy-associated haematologic and gastro-intestinal toxicities were comparable, except for the rate of neutropenia, which increased with amivantamab-chemotherapy compared to chemotherapy alone, but only occurred transiently. Pneumonitis was reported in three percent of patients in the amivantamab-chemotherapy arm.
As a result of the EC approval, the conditional marketing authorisation (MA) for amivantamab, received in December 2021, has been converted to a standard MA.
“We are committed to advancing the science of EGFR-mutated non-small cell lung cancer for patients, with a focus on precision medicine-based approaches that target earlier stage disease,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumours, Johnson & Johnson Innovative Medicine. “Today’s approval marks another important milestone in our pursuit of transforming care for these patients.”
