Frontline Aumolertinib/Chemo Yields PFS Superiority in EGFR+ NSCLC

Adding aumolertinib to chemotherapy in the treatment of patients with EGFR-mutated NSCLC led to improvements in progression-free survival.

Results from the phase 3 ACROSS 2 trial (NCT04500717) revealed that aumolertinib plus chemotherapy significantly improved progression-free survival (PFS) vs aumolertinib monotherapy in the frontline therapy of patients with EGFR-mutated non–small cell lung cancer (NSCLC) harboring concomitant tumor suppressor gene (TSG) alterations.¹

At a median follow-up of 25.3 months, PFS events occurred in 53.4% of patients (n = 63). The investigator-assessed median PFS was 19.8 months with the addition of carboplatin/pemetrexed to aumolertinib vs 16.5 months with aumolertinib alone (HR, 0.55; 95% CI, 0.34-0.91; P = .021).

“The combination of aumolertinib with carboplatin-pemetrexed results in statistically significant improvement of median PFS compared with monotherapy in these patients,” lead study Jie Wang, MD, PhD, shared in a presentation of the data at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.

Wang is the vice chief of Medical Oncology at the Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing, China.

ACROSS 2 Study Breakdown

The ACROSS 2 trial is a phase 3, prospective, multicenter, randomized study designed to evaluate the efficacy and safety of aumolertinib in combination with chemotherapy compared with aumolertinib alone in patients with NSCLC harboring EGFR mutations and concomitant tumor suppressor gene alterations.

Eligible patients include those 18 years of age or older with stage IIIB to stage IV next-generation sequencing–confirmed EGFR-mutated NSCLC who have not received prior systemic therapy for advanced disease. However, prior treatment of adjuvant, neoadjuvant treatment, and concurrent radiochemotherapy is allowed if at least 6 months have passed since the completion of therapy.² Additionally, patients are also required to have an ECOG performance status of 0 or 1 and could have asymptomatic central nervous system metastases.¹

Furthermore, patients on the study were randomly assigned 1:1. In the experimental arm, patients receive aumolertinib at 110 mg orally once daily in combination with pemetrexed (500 mg/m² intravenously [IV] on day 1 of each 3-week cycle) plus carboplatin (area under the curve 5 on day 1 of each cycle) for 4 to 6 cycles. This is followed by maintenance therapy with pemetrexed until disease progression or unacceptable toxicity. In the control arm, patients receive aumolertinib at 110 mg orally once daily as monotherapy, continued until disease progression or unacceptable toxicity.

The primary end point is investigator-assessed PFS per RECIST 1.1 criteria. Secondary end points include overall survival (OS), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety/tolerability outcomes.

Subgroup Analysis

By mutational subgroup, patients with TP53 co-mutations achieved a median PFS of 18.7 months with aumolertinib plus carboplatin/pemetrexed vs 16.3 months with aumolertinib monotherapy (HR, 0.55; 95% CI, 0.33-0.93; P = .024). In those with EGFR exon 19 deletions (19DEL), median PFS was not reached with the combination vs 16.3 months with monotherapy (HR, 0.46; 95% CI, 0.21-0.99; P = .055). For patients harboring EGFR L858R mutations, the median PFS was 18.7 months with the combination vs 16.5 months with aumolertinib alone (HR, 0.63; 95% CI, 0.33-1.20; P = .154).

Across the study population, the ORR was 70.4% in the combination arm compared with 67.2% in the monotherapy arm. The DCR was 92.6% vs 98.4%, respectively.

Safety Findings

In the combination arm (n = 54), the most common treatment-emergent adverse effects (TEAEs) observed in at least 20% of patients included anemia (any-grade, 61.1%; grade ≥3, 7.4%), decreased white blood cell count (53.7%; 9.3%), increased aspartate aminotransferase (AST; 51.9%; 1.9%), increased alanine aminotransferase (ALT; 48.1%; 5.6%), and decreased neutrophil count (44.4%; 20.4%). Other frequently reported TEAEs were increased creatine kinase (any-grade, 27.8%), rash (27.8%), nausea (24.1%), decreased platelet count (22.2%), increased serum creatinine (22.2%), and constipation (20.4%).

Patients treated with aumolertinib monotherapy (n = 64) had lower rates of TEAEs overall. Specifically, the most common any-grade TEAEs observed included increased creatine kinase (42.2%), increased AST (26.6%), rash (20.3%), and increased ALT (18.8%).

References

1. Wang J. Aumolertinib plus chemotherapy for NSCLC with EGFR and concomitant tumor suppressor genes (ACROSS 2): phase III study. Presented at: IASLC 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract 2205.
2. Aumolertinib plus chemotherapy as first-line treatment in patients with EGFR concomitant tumor suppressor gene mutation (ACROSS2). ClinicalTrials.gov. Updated August 5, 2020. Accessed September 7, 2025. https://www.clinicaltrials.gov/study/NCT04500717