|
|
Phase III Study to Determine Efficacy of Durvalumab in Stage II-III Non-small Cell Lung Cancer (NSCLC) After Curative Intent Therapy. - Full Text View - ClinicalTrials.gov
MERMAID-2 （NCT04642469）是一项III期研究，在该研究中，接受标准手术切除的II-III期NSCLC患者在完成治疗意向治疗后进行连续长达2年ctDNA分析，如果ctDNA呈阳性，他们将被随机分配接受辅助度伐利尤单抗（durvalumab）或安慰剂治疗长达2年。首要研究终点是PD-L1≥1%患者的PFS。
In patients with resected, stage II-III NSCLC, the 5-year disease-free survival (DFS) rate with SoC adjuvant chemotherapy is ∼40%. Despite advances with immunotherapy (IO) in the metastatic setting, overall survival (OS) rates for patients with recurrence remain low. Detection of minimal residual disease (MRD), as indicated by circulating tumor DNA (ctDNA), may indicate the presence of clinically indiscernible residual tumor following curative-intent therapy and enable earlier therapeutic intervention, thereby improving outcomes in patients at highest risk of recurrence. In the phase III PACIFIC trial, consolidation durvalumab improved survival outcomes in patients with unresectable, stage III NSCLC without detectable disease progression after curative-intent chemoradiotherapy (Antonia, 2018), suggesting MRD is vulnerable to additional therapy, particularly IO, a concept supported by recent data in MRD+ patients (Moding, 2020). MERMAID-2 will assess the efficacy and safety of durvalumab, versus placebo, in patients with resected, stage II-III NSCLC who become MRD+ after curative-intent therapy.
Trial design
MERMAID-2 (NCT04642469) is a global, phase III, double-blind multicenter study that is currently recruiting patients. Patients with histologically confirmed EGFR/ALK wild-type stage II-III NSCLC who have completed curative-intent therapy (complete resection + optional neoadjuvant and/or adjuvant therapy) will be enrolled in a 96-week surveillance period. During this period, patients will be monitored regularly for MRD emergence via ctDNA analysis of plasma samples, based on personalized MRD panels. Patients who become MRD+ during the surveillance period will be further evaluated to confirm eligibility (no disease recurrence visible on imaging; known PD-L1 status) and ∼284 MRD+ patients will be randomized 1:1 to receive durvalumab 1500 mg IV or placebo q4w, up to 24 months or until investigator-assessed disease recurrence. The primary endpoint is DFS in patients with PD–L1 tumor cell expression ≥1%. Secondary endpoints include DFS in the full analysis set, progression-free survival, OS, time to subsequent therapy, patient-reported outcomes, and safety.
|
|
