Background: Previous studies have shown that there are different methods used to detect the epidermal growth factor receptor (EGFR) mutation status in plasma cell-free DNA (cfDNA) for advanced lung adenocarcinoma patients including the ADx-Amplification Refractory Mutation System (ADx-ARMS). We explored the performance of the ADx-ARMS in detecting the EGFR mutations in cfDNA. Methods: This prospective cohort study enrolled patients who presented with advanced (stage IIIb/IV) lung adenocarcinoma. EGFR mutations in plasma cfDNA and tumor tissues by ADx-ARMS were detected. Next-generation sequencing (NGS) in plasma was performed in patients with inconsistent gene region mutations in the plasma and matched tissue samples. We calculated the clinical parameters of the ADx-ARMS for EGFR mutation status in the plasma of cfDNA, using the tumor tissues as the standard for measurement. The objective response rate (ORR) and progression-free survival (PFS) were also calculated for patients receiving first-generation EGFR-tyrosine kinase inhibitors (TKIs) therapy. Results: In total, 203 patients were included in the final analysis. Mutations were discovered in 58.6% (119/203) of the tumor tissues and 31.0% (63/203) were detected EGFR mutations in both tumor tissues and matched plasma. The sensitivity and the specificity setting for detecting the EGFR mutations in the plasma using the ADx-ARMS were configured to 52.9% and 98.8%. An ORR of 64.8% was observed among the 71 patients who were identified as being EGFR-positive in their tumor tissues, who had received treatments using Gefitinib or Icotinib. Next, the ORR was observed to be 69.0% among the 42 patients with an EGFR mutation in their plasma. The median PFS of the patients with an EGFR mutation in tumor tissues and plasma were 10.0 vs. 11.0 months (P=0.175). The median PFS of the patients with an EGFR wild-type in the plasma was 8.7 months, which was significantly shorter than the EGFR mutant-type in plasma (P=0.001). Conclusions: Using ADx-ARMS as an approach with high specificity but moderate sensitivity to detect the EGFR mutations in plasma cfDNA and EGFR mutation status in plasma cfDNA using the ADx-ARMS can predict the tumor response for EGFR-TKIs.

The safety and immunogenicity of a protein-based tetravalent vaccine SCTV01E that contains spike protein ectodomain (S-ECD) of Alpha, Beta, Delta and Omicron BA.1 are assessed and compared with bivalent protein vaccine SCTV01C (Alpha and Beta variants) and monovalent mRNA vaccine (NCT05323461). The primary endpoints are the geometric mean titers (GMT) of live virus neutralizing antibodies (nAb) to Delta (B.1.617.2) and Omicron BA.1 at day 28 post-injection. The secondary endpoints include the safety, day 180 GMTs against Delta and Omicron BA.1, day 28 GMTs to BA.5, and seroresponse rates of neutralizing antibodies and T cell responses at day 28 post-injection. 450 participants, comprising of 449 males and 1 female, with a median age (range) of 27 (18–62) years, are assigned to receive one booster dose of BNT162b2, 20 µg SCTV01C or 30 µg SCTV01E and completed 4-week follow-up. All SCTV01E related adverse events (AEs) are mild or moderate and no Grade ≥3 AE, serious AE or new safety concerns are identified. Day 28 GMT of live virus neutralizing antibodies and seroresponse against Omicron BA.1 and BA.5 with SCTV01E are significantly higher than those with SCTV01C and BNT162b2. These data indicate an overall neutralization superiority with tetravalent booster immunization in men.