Actively Recruiting
A ctDNA-guided Phase II Trial of Osimertinib Combined with Sacituzumab Tirumotecan in EGFR-mutated Advanced Non-Small Cell Lung Cancer Patients with Positive ctDNA After Osimertinib Monotherapy
Led by Guangdong Association of Clinical Trials · Updated on 2026-05-26
120
Participants Needed
4
Research Sites
26 weeks
Total Duration
On this page
AI-Summary
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 mg/kg 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.
CONDITIONS
Brief Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at consent, any gender
- Histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC not suitable for surgery or radical radiotherapy
- Presence of sensitizing EGFR mutation (exon 19 deletion and/or L858R)
- Completion of 3 to 5 weeks of first-line osimertinib monotherapy without disease progression and willingness to undergo ctDNA testing
- At least one measurable target lesion by RECIST v1.1
- ECOG Performance Status score of 0 or 1 within 7 days before enrollment
- Adequate organ and bone marrow function as defined by specific blood counts and liver, kidney, and coagulation tests
- Use of effective contraception during treatment and for 6 months after dosing for those of childbearing potential
- Willingness to participate, sign informed consent, and comply with study procedures
You will not qualify if you...
- Presence of squamous cell carcinoma or other specified lung cancer types
- Known meningeal, brainstem, spinal cord metastases or active brain metastases, except certain asymptomatic leptomeningeal metastases
- Prior systemic anti-tumor therapy for advanced NSCLC other than osimertinib
- Previous treatment with any TROP2-targeted or topoisomerase I-targeted therapy
- Other malignancies within 3 years except certain cured local tumors
- Significant cardiovascular or cerebrovascular diseases or recent serious events
- Uncontrolled systemic diseases such as poorly controlled diabetes or hypertension
- History or current pneumonitis/interstitial lung disease requiring steroids or suspected but unruled out
- Severe eye conditions affecting corneal healing
- Severe lung impairment or prior pneumonectomy
- Active inflammatory bowel disease or serious gastrointestinal conditions
- Conditions affecting absorption or metabolism of osimertinib
- Tumor invasion or compression causing symptoms or fistula risk
- Unrecovered toxicities from prior therapy above Grade 1
- Recent serious infections or active infections requiring treatment
- Active hepatitis B or C infection
- Positive HIV or active syphilis infection
- History of organ or stem cell transplantation
- Recent major surgery or planned surgery during study
- Allergy to study drugs or severe hypersensitivity to monoclonal antibodies
- Use of strong CYP3A4 inducers or inhibitors that cannot be discontinued
- Recent high-dose radiotherapy for lung or other lesions
- Recent live vaccinations
- Rapid disease deterioration before first dose
- Pregnancy or breastfeeding
- Any condition interfering with study evaluation or safety as judged by investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 3 to 5 weeks
Participants receive osimertinib monotherapy for 3 to 5 weeks and undergo tumor assessment and ctDNA testing to determine study cohort assignment.
1 baseline visit and tumor assessment after treatment
Duration - Until disease progression or discontinuation
Participants with positive ctDNA receive combined treatment of osimertinib daily and sacituzumab tirumotecan intravenously every 2 weeks until disease progression or other discontinuation criteria are met.
Visits every 2 weeks for sacituzumab tirumotecan infusions and daily oral osimertinib dosing; tumor assessments every 6 weeks during the first year and every 12 weeks thereafter
Duration - Up to 36 months
Participants with negative ctDNA continue osimertinib monotherapy and are observed under routine care with treatment and data collection at physician discretion.
Visit frequency vary as per physician discretion
Trial Site Locations
Total: 4 locations
1
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University
Guangzhou, Guangdong, China, 510080
Actively Recruiting
2
Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences
Meizhou, Guangdong, China, 514031
Actively Recruiting
3
The First Affiliated Hospital of Shantou University Medical College
Shantou, Guangdong, China, 515041
Actively Recruiting
4
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China, 518036
Actively Recruiting
Research Team
Q
Qing Zhou
Y
Yi-Chen Zhang
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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