Phase II Study of Osimertinib Combined with Sacituzumab Tirumotecan for EGFR-Mutated Advanced Non-Small Cell Lung Cancer Patients with Positive ctDNA After Initial Osimertinib Treatment

What this Trial Is About

Researchers are studying patients with advanced non-small cell lung cancer NSCLC who have a specific mutation in the EGFR gene and who do not clear circulating tumor DNA ctDNA after initial treatment with osimertinib alone. The goal is to explore the effectiveness and safety of combining osimertinib with sacituzumab tirumotecan in these patients. This is a phase II, multicenter, ctDNA-guided clinical trial that divides patients into groups based on their ctDNA status after initial osimertinib treatment. Participants first receive one cycle 3 to 5 weeks of osimertinib monotherapy at a standard oral dose of 80 mg daily. After this, tumor assessment and ctDNA testing determine their study group. Those with positive ctDNA results join Cohort 1, receiving osimertinib plus intravenous sacituzumab tirumotecan 4 mgkg every two weeks until disease progression, unacceptable side effects, or other criteria for stopping treatment. Those with negative ctDNA results continue osimertinib alone in Cohort 2, which is observational and allows physicians to manage treatment as usual. During the study, participants undergo regular tumor evaluations using imaging according to RECIST v1.1 criteria every six weeks in the first year and every 12 weeks thereafter, up to 36 months. Researchers monitor progression-free survival, response rates, overall survival, and adverse events. The study also collects safety data up to 30 days after treatment ends. Total participation can last up to three years depending on individual outcomes and treatment continuation.

A ctDNA-guided Phase II Trial of Osimertinib in Combination With Sacituzumab Tirumotecan in EGFR-mutated Advanced NSCLC Patients With Positive ctDNA After lead-in Osimertinib Monotherapy