EMA Accepts Marketing Authorization Application for Aumolertinib in EGFR-Mutated NSCLC

Pharmaceutical manufacturer EQRx announced December 2, 2022, that the European Medicines Agency has accepted a marketing authorization application for the use of aumolertinib in EGFR-mutated non–small cell lung cancer and locally advanced or metastatic EGFR T790M mutation–positive NSCLC.

Vince Miller, MD

Pharmaceutical manufacturer EQRx announced December 2, 2022, that the European Medicines Agency (EMA) has accepted a marketing authorization application (MAA) for the use of aumolertinib in EGFR-mutated non–small cell lung cancer (NSCLC) and locally advanced or metastatic EGFR T790M mutation–positive NSCLC.1

The MAA is based on data from the pivotal phase 3 ANEAS trial (NCT03849768) evaluating the third-generation EGFR TKI vs gefitinib (Iressa) for first-line treatment of locally advanced or metastatic EGFR-mutated NSCLC. At a median follow-up of 20.5 months (95% CI, 18.0-20.6) for aumolertinib and 20.7 months (95% CI, 19.3-20.8) for gefitinib, the median duration of progression-free survival (PFS) was 19.3 months (95% CI, 17.8-20.8) and 9.9 months (95% CI, 8.3-12.6), respectively (HR, 0.46; 95% CI, 0.36-0.60; P <.0001).2

PFS rates favored the experimental arm at 1 year (69.5% vs 46.3%) and at 2 years (32.5% vs 12.9%. Investigators found that the PFS benefit inuced by aumolertinib was consistent across all prespecified stratification factors, including EGFR mutation type and central nervous system (CNS) metastases status.

“For patients with locally advanced or metastatic NSCLC with EGFR mutations, third generation EGFR-TKIs have become the standard of care in many places worldwide,” Vince Miller, MD, physician-in-chief at EQRx, said in a news release. “However, these treatments are often not easily attainable for patients, and there remains a need for additional third-generation EGFR TKIs to increase treatment options and improve access to therapies for people with non-small cell lung cancer.”

According to the European Commission, lung cancer accounted for 20.4% of all cancer deaths in the 27-member European Union in 2020. Lung was the fourth most common malignancy and the leading cause of cancer death.3 NSCLC accounts for 85% of cancers worldwide. In Europe, 14.1% of those cancers harbor EGFR mutations.4

In this randomized, double-blind trial, investigators enrolled 429 patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC and an EGFR mutation at 53 locations in China. Permitted EFGR mutations included sensitizing mutations, such as exon 19 deletions and L858R mutations, as detected by a central laboratory. Patients were required to have at least 1 measurable lesion of at least 10 mm per RECIST v1.1 criteria.

Those with asymptomatic and stable CNS metastases that did not require steroids for at least 2 weeks before the initiation of the study drug were permitted. However, those who had received prior systemic therapy, including prior treatment with an EGFR inhibitor, were excluded. Previous treatment in the adjuvant/neoadjuvant setting was allowed.

Patients were randomly assigned to 110 once-daily aumolertinib (n = 214) or 250 mg once-daily gefitinib (n = 215). Investigators stratified patients by type of EGFR mutation (exon 19 deletion vs L858R) and CNS metastases status (with vs without). Patients received treatment with the study drug until disease progression, withdrawal of consent, unacceptable toxicity, or other discontinuation criteria were met.

Treatment with the study drug was permitted beyond disease progression if patients continued to derive clinical benefits per treating investigator assessment. Patients in the gefitinib arm who acquired an EGFR T790M mutation were eligible to cross over to the aumolertinib arm.

The primary end point of the trial was investigator-assessed PFS. Secondary end points included overall survival, objective response rate, duration of response, disease control rate, and depth of response.

Nearly all (98.8%) patients experienced at least 1 adverse effect (AE) during study treatment. Investigators observed any-cause grade 3 or higher AEs noted in 36.4% of the aumolertinib arm and 35.8% of the gefitinib arm.

Although increased rates of blood creatine phosphokinase were common with aumolertinib, only 7% of the patients in this arm had a blood creatine phosphokinase increase of grade 3 or higher. No patients experienced increases associated with rhabdomyolysis, and blood creatine phosphokinase increase was not observed as a serious AE. Additionally, although increases led to temporary aumolertinib interruption in 5.1% (n = 11) of patients and dose reduction in 2.8% (n = 6) of patients, it caused no instances of aumolertinib discontinuation.

This is EQRx’s second submission to a regulatory agency for aumolertinib. The United Kingdom’s Medicines and Healthcare Products Regulatory Agency is currently reviewing an MAA for the treatment of EGFR-mutated NSCLC.


  1. EQRx announces acceptance of marketing authorization application by the European Medicines Agency for aumolertinib in EGFR-mutated non-small cell lung cancer. News release. December 2, 2022. Accessed December 2, 2022. https://bit.ly/3EUnErf
  2. Lu S, Dong X, Jian H, et al. AENEAS: a randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non–small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol. 2022;40(27):3162-3171. doi:10.1200/JCO.21.02641
  3. Dyba T, et al. The European cancer burden in 2020: Incidence and mortality estimates for 40 countries and 25 major cancers. Eur J Cancer. 2021;157:308-347.
  4. Zhang, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7:78985-78993. doi:10.18632/oncotarget.12587
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