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

NCT07375316 | Recruiting Phase 2

• 1 other identifier: CTONG2509
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  From date of start of combinational treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.

Secondary Outcomes (5)

• Overall Response Rate (ORR) in Cohort 1, Assessed by Investigator

  Tumour assessments will be conducted according to the RECIST v1.1, with valuations performed every six weeks during the first year after first dose and every 12 weeks thereafter, up to 36 months.

• Disease Control Rate (DCR) in Cohort 1, Assessed by Investigator

  Tumour assessments will be conducted according to the RECIST v1.1, with valuations performed every six weeks during the first year after first dose and every 12 weeks thereafter, up to 36 months.

• Overall Survival (OS) in Cohort 1

  From date of start of combinational treatment until the date of death from any cause, assessed up to 36 months

• Adverse Events in Cohort 1

  From the start of study drug to 30 days after the last dose of study drug

• Progression-free survival in Cohort 2, Assessed by Investigator

  From date of start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Other Outcomes (1)

• Biomarkers in Cohort 1

  The data of ctDNA clearance rate will be collected at 2 time points: at the completion of induction treatment with osimertinib, and 6 weeks after first dose of study treatment.

Study Arms (2)

Cohort 1: （experimental cohort）Osimertinib + Sacituzumab Tirumotecan

EXPERIMENTAL

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 + Sacituzumab Tirumotecan

Cohort 2: （observational cohort）Osimertinib monotherapy

ACTIVE COMPARATOR

Drug: Osimertinib •Osimertinib (80mg QD).

Drug: Osimertinib

Interventions

Osimertinib + Sacituzumab Tirumotecan DRUG

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

Cohort 1: （experimental cohort）Osimertinib + Sacituzumab Tirumotecan

Osimertinib DRUG

Osimertinib (80mg QD)

Cohort 2: （observational cohort）Osimertinib monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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);
• Other malignancies (except cured local tumors, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, carcinoma in situ of the cervix) within 3 years prior to enrollment;
• Presence of any of the following cardiovascular and cerebrovascular diseases or risk factors:
• Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, Class III or IV heart failure \[according to New York Heart Association (NYHA) classification\], symptomatic or poorly controlled serious arrhythmia, cerebrovascular accident, transient ischemic attack, and other serious cardiovascular and cerebrovascular diseases within 6 months prior to enrollment;
• Previous history of myocardial diseases such as myocarditis, primary cardiomyopathy and specific cardiomyopathy;
• Any peripheral arterial thromboembolic event, pulmonary embolism, deep vein thrombosis, or other serious thromboembolic event within 3 months prior to enrollment;
• Major vascular disease such as aortic aneurysm, aortic dissecting aneurysm that may be life-threatening or require surgery within 6 months prior to first dose;
• Mean corrected QT interval (QTcF) between ventricular depolarization to repolarization \> 470 ms;
• Uncontrolled systemic disease as judged by the investigator:
• Poorly controlled diabetes mellitus (two consecutive fasting glucose ≥10 mmol/L);
• Poorly controlled hypertension (systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg);
• Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage (\> 1 time/week);

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (4)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University

Guangzhou, Guangdong, 510080, China

RECRUITING

Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences

Meizhou, Guangdong, 514031, China

RECRUITING

The First Affiliated Hospital of Shantou University Medical College

Shantou, Guangdong, 515041, China

RECRUITING

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Qing Zhou

CONTACT

+51221 862083827812; gzzhouqing@126.com

Yi-Chen Zhang

CONTACT

+51221 862083827812

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 29, 2026
• Study Start: December 15, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)