New results from the phase III ACROSS 2 trial demonstrated that aumolertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI), combined with platinum-pemetrexed chemotherapy significantly improved progression-free survival (PFS) compared with aumolertinib monotherapy in patients with advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR-sensitizing mutations and concomitant tumor suppressor gene mutations. The results were presented by Jie Wang, MD, of the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital in China, at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract PL02.06).
Patients with EGFR concomitant mutations typically face a poor prognosis and, until now, have had no standard treatment regimen in clinical practice. Previous studies have suggested that an EGFR TKI combined with chemotherapy may provide better efficacy than an EGFR TKI alone. ACROSS 2 is the first global, multicenter, open-label, randomized, controlled phase III trial to address this question, according to Dr. Wang.
Study Design
ACROSS 2 (ClinicalTrials.gov identifier NCT04500717) investigators enrolled patients with histologically confirmed stage IIIB or IV NSCLC harboring EGFR-sensitizing mutations and tumor suppressor gene mutations; they had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned 1:1 to receive either aumolertinib at 110 mg daily plus carboplatin (AUC = 5) and pemetrexed at 500 mg/m² every 3 weeks or aumolertinib monotherapy until disease progression. Stratification factors included EGFR mutation type (Ex19del/L858R) and presence of central nervous system metastases. Baseline characteristics were well balanced between treatment arms. The primary endpoint of the trial was PFS; secondary endpoints included objective response rate, disease control rate, duration of response, overall survival, and safety.
Key Findings
The median follow-up was 25.3 months. The median PFS was 19.8 months with the combination of aumolertinib and chemotherapy vs 16.5 months with aumolertinib monotherapy (hazard ratio = 0.55, 95% confidence interval = 0.339–0.910, P = .0205). Overall survival data remain immature.
The most common treatment-emergent adverse events (occurring in ≥ 20% of patients) with aumolertinib included decreased white blood cell count, decreased neutrophil count, decreased platelet count, anemia, aspartate aminotransferase and alanine aminotransferase increase, increased creatine kinase, increased serum creatinine, nausea, constipation, and rash.
Dr. Wang reported that the addition of chemotherapy did not seem to alter aumolertinib’s safety profile, and no new safety signals were observed.
“This phase III trial provides the first evidence that aumolertinib combined with platinum-pemetrexed [chemotherapy] offers a statistically significant PFS benefit over monotherapy for this patient population, with a manageable safety profile,” she said.
Disclosure: For full disclosures of the study authors, visit cattendee.abstractsonline.com.
