Neoadjuvant sacituzumab tirumotecan with or without osimertinib for resectable EGFR‑mutated non‑small cell lung cancer

A Randomized, Open-label, Multicenter, Phase II Clinical Study to Evaluate the Safety and Efficacy of Sacituzumab Tirumotecan in Combination With Osimertinib or as Monotherapy for Neoadjuvant Treatment in Patients With Resectable Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer

This trial will test whether giving sacituzumab tirumotecan alone or together with osimertinib before surgery helps people with resectable EGFR‑mutated non‑small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: sacituzumab, osimertinib, prednisone
• Locations: 1 site (Beijing)
• Trial ID: NCT07329322 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label, multicenter Phase 2 study testing sacituzumab tirumotecan either alone or combined with the EGFR inhibitor osimertinib as preoperative (neoadjuvant) therapy in patients with resectable EGFR‑mutated non‑small cell lung cancer. Participants who meet eligibility will be assigned to one of the treatment arms and receive study drugs prior to planned surgical resection. The trial will monitor safety, tolerability, and measures of anti‑tumor activity such as tumor shrinkage and pathological response at surgery. Outcomes will inform whether this combination or monotherapy can improve surgical outcomes and short‑term disease control in this patient population.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed, resectable NSCLC harboring EGFR sensitizing mutations, ECOG 0–1, no prior systemic or local therapy, and adequate organ function are the intended participants.

Not a fit: Patients with unresectable or metastatic disease, prior systemic therapy for lung cancer, unsuitable organ function, or who cannot tolerate EGFR‑targeted therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the treatment could shrink tumors before surgery, increase the chance of a more complete resection, and lower early recurrence risk.

How similar studies have performed: Osimertinib has shown strong activity in EGFR‑mutant NSCLC and antibody–drug conjugates have been effective in other settings, but using sacituzumab tirumotecan together with osimertinib as preoperative therapy is largely novel.

Eligibility criteria

Inclusion Criteria:

1. Male or female, ≥ 18 and ≤ 75 years at the time of signing the informed consent form (ICF).
2. Histologically or cytologically confirmed NSCLC.
3. No prior systemic anti-tumor therapy.
4. No prior local therapy for NSCLC.
5. Confirmed by tumor histology, or cytology to have EGFR sensitizing mutations.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.
7. At least one target lesion as assessed by the investigator according to RECIST v1.1.
8. Life expectancy ≥ 24 weeks.
9. Adequate organ and bone marrow function.
10. For female participants of childbearing potential and male participants with partners of childbearing potential, they must agree to use effective medical contraception from the start of signing the ICF until 6 months after the last dose.
11. Participants must voluntarily join this study, sign the ICF, and be able to comply with the protocol-specified visits and related procedures.

Exclusion Criteria:

1. Tumor histology or cytology confirming combined small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma or squamous cell carcinoma components of more than 10%.
2. Participants with other malignant tumors within 3 years prior to randomization.
3. Resting electrocardiogram (ECG) showing clinically significant abnormal results.
4. Presence of any of the following cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors.
5. Uncontrolled systemic diseases in the investigator's judgment.
6. History of interstitial lung disease (ILD), drug-induced ILD, or non-infectious pneumonitis, have current ILD or non-infectious pneumonitis.
7. Clinically severe lung damage due to complications of lung disorder.
8. Participants who have received systemic corticosteroids therapy with \> 10 mg/day of prednisone or other immunosuppressive drugs within 2 weeks before randomization.
9. Known active pulmonary tuberculosis.
10. Known history of allogeneic organ transplant and allogeneic hematopoietic stem cell transplant.
11. Active hepatitis B.
12. Positive for human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
13. Known hypersensitivity to osimertinib, sacituzumab tirumotecan, or any of their components (including but not limited to polysorbate-20); known history of severe hypersensitivity to other biologics.
14. Have received a live vaccine within 30 days prior to randomization, or plan to receive a live vaccine during the study.
15. Pregnant or lactating women.
16. Any condition that, in the investigator's opinion, would interfere with the evaluation of the study drug, participant safety, or interpretation of study results, or any other condition that the investigator considers unsuitable for participation in this study.

Where this trial is running

Beijing

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Yina Diao

Conditions Non-Small Cell Lung Cancer