A ctDNA-guided Phase II Trial of Osimertinib in Combination With Sacituzumab Tirumotecan in EGFR-mutated Advanced NSCLC Patients With Positvie ctDNA After lead-in Osimertinib Monotherapy
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-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);
• ≥1 measurable target lesion per RECIST v1.1;
• ECOG Performance Status score of 0 or 1 within 7 days before enrollment;
• Adequate organ and bone marrow function (no blood transfusion, recombinant human thrombopoietin, or colony stimulating factor therapy within 2 weeks prior to the first dose), defined as follows:
‣ Hematology: neutrophil count (NEUT) ≥ 1.5×109/L; platelet (PLT) ≥ 100×109/L; hemoglobin(Hb) ≥ 90g/L;
⁃ Liver function: AST and ALT ≤ 2.5× ULN (if liver metastases are present, ≤5 × ULN); total bilirubin (TBIL) ≤ 1.5×ULN (if liver metastases are present, ≤3 × ULN); serum albumin ≥30g/L;
⁃ Renal function: serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (calculated using the standard Cockcroft-Gault formula);
⁃ Coagulation function: international normalized ratio (INR), activated partial thromboplastin time (APTT) and prothrombin time (PT) ≤ 1.5× ULN;
• Use of effective medical contraception during the study treatment period and for 6 months after the end of dosing for female subjects of childbearing potential and male subjects with partners of childbearing potential;
• Willingness to participate in the study, sign the ICF, and comply with the protocol-specified visits and relevant procedures.