UK’s MHRA Accepts Marketing Authorization Application for Aumolertinib in EGFR+ NSCLC

Non–Small Cell Lung Cancer

The United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has accepted for review the marketing authorization application for aumolertinib, a third-generation EGFR TKI, for the first-line treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with activating EGFR mutations and for the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation–positive NSCLC.¹

The application is based on findings from pivotal phase 3 AENEAS trial (NCT03849768), where frontline aumolertinib demonstrated a statistically significant improvement in progression-free survival (PFS) vs gefitinib (Iressa) in this patient population (HR, 0.46; 95% CI, 0.36-0.60; P < .0001), meeting the primary end point of the study.² The median PFS with aumolertinib was 19.3 months (95% CI, 17.8-20.8) vs 9.9 months (95% CI, 8.3-12.6) with gefitinib.

“This acceptance of the marketing authorization application for aumolertinib by the MHRA is our first regulatory filing and a significant milestone for EQRx,” Melanie Nallicheri, president and chief executive officer of EQRx, stated in a press release. “In the UK, approximately 39,000 people are diagnosed with lung cancer each year, and about 10% to 15% of these patients have EGFR-sensitizing mutations. Given its promising clinical activity and tolerability profile, we believe that, if approved, aumolertinib would represent an additional and differentiated treatment option for patients in the UK who have EGFR-mutated NSCLC.

Aumolertinib is approved by the National Medical Products Administration of China for both first- and second-line treatment of patients with locally advanced or metastatic EGFR-mutated NSCLC.

The randomized, double-blind, multicenter AENEAS trial, which was conducted across 53 sites in China, evaluated the efficacy and safety of aumolertinib vs gefitinib (Iressa) as first-line treatment for adults with locally advanced or metastatic EGFR-mutated NSCLC. Notably, patients with stable, asymptomatic central nervous system (CNS) metastases were eligible for enrollment.

The study enrolled 429 patients who were randomized to receive 110 mg of aumolertinib (n = 214) or 250 mg of gefitinib (n = 215) once daily. The primary end point was PFS per investigator assessment, and secondary end points included overall survival, overall response rate (ORR), and safety.

The ORR and disease control rate (DCR) were similar in the aumolertinib and gefitinib arms (ORR, 73.8% and 72.1%, respectively; DCR, 93.0% and 96.7%, respectively). The median duration of response (DOR) was 18.1 months (95% CI, 15.2–not applicable [NA]) with aumolertinib vs 8.3 months (95% CI, 6.9-11.1) with gefitinib (HR, 0.38; 95% CI, 0.28-0.51; P < .0001).

Grade 3 or greater adverse effects of any cause occurred in 36.4% and 35.8% of patients in the aumolertinib and gefitinib arms, respectively. Any-grade rash and diarrhea were experienced by 23.4% and 16.4% of patients who received aumolertinib vs 41.4% and 35.8% of those who received gefitinib, respectively.

Additionally, of 429 patients, 106 (aumolertinib, n = 51; gefitinib, n = 55) had baseline CNS metastases (CNS full analysis set; cFAS) and 60 patients (aumolertinib, n = 28; gefitinib, n = 32) had baseline CNS target lesions (CNS evaluable-for-response set; cEFS) per RECIST v1.1 criteria by blinded independent central review.

Additional results from the study, which were presented at the 2022 ASCO Annual Meeting, demonstrated comparable activity between the subgroup of patients with CNS metastases and the overall population.

At the cutoff date of August 6, 2021, and based on the cEFS population, CNS PFS events occurred in 10 patients (35.7%) in the aumolertinib arm vs 20 patients (62.5%) in the gefitinib arm.³ Treatment with aumolertinib led to a significant improvement in median CNS PFS compared with gefitinib (29.0 vs 8.3 months; HR, 0.268; 95% CI, 0.119-0.605; P = 0.0007).

The estimated 12- and 18-month CNS PFS rates were 73.5% (95% CI, 52.2%-86.5%) and 64.9% (95% CI, 43.0%-80.1%) in aumolertinib arm vs 23.1% (95% CI, 8.5%-41.8%) and 0% in gefitinib arm. The confirmed CNS ORRs were 85.7% (95% CI, 67.3%-96.0%) and 75.0% (95% CI, 56.6%-88.5%) in patients treated with aumolertinib and gefitinib, respectively (odds ratio, 2.000; 95% CI, 0.531-7.539; P = 0.3059).

The CNS DCR was 92.9% (95% CI, 76.5%-99.1%) with aumolertinib vs 96.9% (95% CI, 83.8%-99.9%) with gefitinib (odds ratio, 0.419; 95% CI, 0.036-4.891; P = .4881). The median CNS DOR was 27.7 months (95% CI, NA-NA) and 6.9 months (95% CI, 5.5-9.4), respectively (HR, 0.160; 95% CI, 0.058-0.441; P < .0001).

Aumolertinib also elicited prolonged median CNS PFS compared with gefitinib in the cFAS population (29.0 vs 8.3 months; HR, 0.319; 95% CI, 0.176-0.580; P < .0001).

The safety profile in the population with CNS metastases was consistent with that reported in the overall population.

Additional randomized studies of aumolertinib are ongoing including the phase 3 ATTACK trial (NCT04870190), which is investigating the agent vs osimertinib (Tagrisso) as second-line therapy in patients with advanced EGFR-mutated NSCLC and CNS metastases.

“We aim to expand access to third generation EGFR inhibitors and look forward to working with the MHRA as it conducts its review,” Nallicheri concluded.

References

1. EQRx Announces Acceptance of Marketing Authorization Application by the UK's Medicines and Healthcare Products Regulatory Agency for Aumolertinib in EGFR-Mutated Non-small Cell Lung Cancer. News release. June 14, 2022. Accessed June 22, 2022. https://bit.ly/3QCfqsT
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. Published online May 17, 2022. doi:10.1200/JCO.21.02641
3. Lu S, Dong X, Jian H, et al. Aumolertinib activity in patients with CNS metastases and EGFR-mutated NSCLC treated in the randomized double-blind phase III trial (AENEAS). J Clin Oncol. 2022;40(suppl 16):9096. doi:10.1200/JCO.2022.40.16_suppl.9096