NCT07375316

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Guangdong Association of Clinical Trials · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This is an investigator-initiated, multicenter, ctDNA-guided phase II study to evaluate 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 (Cohort 1). Patients screened to be with negative ctDNA after lead-in osimertinib will be prospectively enrolled in a real-world cohort to observe PFS on continued osimertinib monotherapy (Cohort 2). Approximately 120 eligible patients are planned to undergo tumor assessment and ctDNA testing upon completion of one cycle (3 weeks per cycle) treatment with osimertinib (obtained commercially at the standard dose of 80mg orally daily). Patients without disease progression assessed by imaging will be enrolled into different study cohorts based on ctDNA test results. Only patients who test positive for ctDNA will be enrolled in Cohort 1 of the clinical study to receive the combinational treatment of intravenous sac-TMT at a fixed dose of 4mg/kg every 2 weeks plus oral osimertinib also at a fixed dose of 80mg daily until disease progression, death, unacceptable toxicity, or another treatment discontinuation criterion is met, whichever occurs first. Patients who test negative for ctDNA will continue to receive osimertinib monotherapy and be prospectively enrolled in observational Cohort 2. In this observational cohort, treatments and treatment-related data collection are at the discretion of physicians.

Conditions

• Non Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Osimertinib + Sacituzumab Tirumotecan	Osimertinib (80mg QD) + Sacituzumab Tirumotecan (4 mg/m2) on Day 1 and Day 8 of 28-day cycles (4 mg/m2 Q2W).
DRUG	Osimertinib	Osimertinib (80mg QD)

Timeline

• Start date: 2025-12-15
• Primary completion: 2028-06-30
• Completion: 2028-12-30
• First posted: 2026-01-29
• Last updated: 2026-02-10

Locations

4 sites across 1 country: China