Phase II Study of Sacituzumab Tirumotecan in Combination With Osimertinib or Sacituzumab Tirumotecan for Neoadjuvant Treatment in Patients With Resectable Epidermal Growth Factor Receptor (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

The aim of the 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.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Osimertinib; Drug: Sacituzumab Tirumotecan

Detailed Description

This is a randomized, open-label, multicenter, Phase 2 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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yina Diao; Phone Number: 028-67252634; Email: diaoyina@kelun.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Hospital Chinese Academy of Medical Sciences
    • Contact: Jie He; Jie Wang; Phone Number: 010-87788207; 010-87788021; Email: hejie@cicams.ac.cn; wangjiegcp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacituzumab Tirumotecan+Osimertinib; Participants will receive Sacituzumab Tirumotecan for each 2-week cycle, Osimertinib once-daily for each 2-week cycle.	Drug: Osimertinib; 80mg, QD; Drug: Sacituzumab Tirumotecan; Sacituzumab Tirumotecan: 4mg/kg, intravenous (IV) infusion
Experimental: Sacituzumab Tirumotecan; Participants will receive Sacituzumab Tirumotecan for each 2-week cycle	Drug: Sacituzumab Tirumotecan; Sacituzumab Tirumotecan: 4mg/kg, intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) rate	MPR rate is defined as the proportion of participants achieving ≤ 10% residual viable tumor cells in the postoperative surgical specimen.	up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological Complete Response (pCR) rate	pCR rate is defined as the proportion of participants achieving absence of any residual viable tumor cells in the postoperative surgical specimen.	up to 60 months
Residual viable tumor percentage (RVT%)	RVT% is defined as the proportion of residual viable tumor cells in the postoperative surgical specimen.	up to 60 months
R0 resection rate	Proportion of participants achieving R0 resection	up to 60 months
Pathological lymph node downstaging rate	Pathological lymph node downstaging rate is defined as the proportion of participants achieving pathological lymph node downstaging	up to 60 months
Pathological primary tumor downstaging rate	Pathological primary tumor downstaging rate is defined as the proportion of participants achieving pathological primary tumor downstaging	up to 60 months
ORR	ORR is defined as a partial or complete response according to RECIST, version 1.1.	up to 60 months
EFS	EFS is defined as the time from randomization to progression of disease, recurrence of disease, or death from any cause.	up to 60 months
DFS	DFS is defined as the time from surgery to disease progression (recurrence or metastasis) or death due to any cause.	up to 60 months
OS	OS is defined as the time from randomization to death from any cause.	up to 60 moths
Incidence of Adverse events (AEs) and serious adverse events (SAEs) as assessed by NCI CTCAE v5.0	Incidence (based on NCI CTCAE v5.0) of adverse events (AEs) and serious adverse events (SAEs).	up to 60 months
Severity of Adverse events (AEs) and serious adverse events (SAEs) as assessed by NCI CTCAE v5.0	Severity (based on NCI CTCAE v5.0) of adverse events (AEs) and serious adverse events (SAEs).	up to 60 months
Maximum observed plasma concentration (Cmax) of Sacituzumab Tirumotecan-ADC, Sacituzumab Tirumotecan-TAB, and free KL610023	To assess the pharmacokinetic (PK) profile of Sacituzumab Tirumotecan.	up to 60 months
Anti-drug Antibodies (ADA) of Sacituzumab Tirumotecan	Immunogenicity test results of Sacituzumab Tirumotecan.	up to 60 months

Collaborators and Investigators

• Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): October 31, 2032

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: December 26, 2025
• First Posted (Actual): January 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; osimertinib
• Other Study ID Numbers: SKB264-II-18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No