EGFR-mutated advanced NSCLC patients without ctDNA clearance after lead-in osimertinib monotherapy have inferior PFS compared with those with ctDNA clearance. Consequently, these patients might need an intensified therapeutic strategy, such as osimertinib combined with chemotherapy or ADC. This study aims to explore the efficacy and safety of osimertinib in combination with sacituzumab tirumotecan adaptively in EGFR-mutated advanced NSCLC patients with positive ctDNA after lead-in osimertinib monotherapy.
Age ≥18 years at the time of signing the Informed Consent Form (ICF), regardless of gender;
Histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC not amenable to radical surgery and/or radical radiotherapy (regardless of concurrent/sequential chemotherapy) (according to TNM staging of lung cancer published by the Union for International Cancer Control and American Joint Committee on Cancer (UICC/AJCC), 8th edition);
Presence of sensitizing EGFR mutation (exon 19 deletion and/or L858R);
Completion of 3~5-week first-line treatment with osimertinib monotherapy. Non-PD as assessed by investigator per RECIST v1.1, and willing to undergo ctDNA testing (patients with positive ctDNA test results will be enrolled in Cohort 1; patients with negative ctDNA test results will be enrolled in observational Cohort 2);
For NSCLC, histologically or cytologically confirmed squamous cell carcinoma component or presence of coexisting small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma component;
Known presence of meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, and active brain metastases. Patients with asymptomatic, focal leptomeningeal metastases on contrast-enhanced MRI may be eligible if, in the investigator's opinion, no local therapy or dehydration/symptomatic treatment is required;
Prior treatment with systemic anti-tumor therapy for locally advanced or metastatic NSCLC other than osimertinib;
Prior treatment with any TROP2-targeted therapy or any therapy that targets topoisomerase I (including ADCs);
Parallel
Osimertinib + Sacituzumab Tirumotecan
DrugOsimertinib (80mg QD) + Sacituzumab Tirumotecan (4 mg/m2) on Day 1 and Day 8 of 28-day cycles (4 mg/m2 Q2W).
Osimertinib
DrugOsimertinib (80mg QD)
Progression-free Survival (PFS) in Cohort 1, Assessed by Investigator
PFS is defined as time from the date of start of combinational treatment until the date of disease progression per RECIST 1.1, as assessed by investigator, or death due to any cause.
Overall Response Rate (ORR) in Cohort 1, Assessed by Investigator
ORR is defined as the percentage of subjects who have a best overall response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 as assessed by the Investigator.
Disease Control Rate (DCR) in Cohort 1, Assessed by Investigator
DCR is defined as the percentage of subjects who have a best overall response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) per RECIST 1.1 as assessed by the Investigator.
Overall Survival (OS) in Cohort 1
OS is defined as the time from the date of start of combinational treatment until the date of death due to any cause.
Adverse Events in Cohort 1
The number of patients with adverse events and the severity according to CTCAE v5.0.
Biomarkers in Cohort 1
The proportion of patients with circulating tumor DNA clearance after 6 weeks and 12 weeks study treatment.
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