A Study of SYS6010 Combined With Osimertinib Versus Osimertinib Alone as Neoadjuvant Therapy for Patients With EGFR Mutation-positive Resectable Non-squamous Non-small Cell Lung Cancer

A Phase II Study to Evaluate the Safety and Efficacy of SYS6010 Combined With Osimertinib Versus Osimertinib as Neoadjuvant Therapy in Participants With Resectable Stage II-IIIB Non-squamous Non-small Cell Lung Cancer With EGFR Mutation Positive

To evaluate the safety and efficacy of SYS6010 combined with osimertinib as neoadjuvant therapy for patients with resectable EGFR mutation non-squamous non-small cell lung cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: SYS6010; Drug: Osimertinib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Detailed Description

This study includes three stages: a neoadjuvant therapy stage, a surgery stage, and an adjuvant follow-up stage. In the neoadjuvant therapy stage, eligible participants will be stratified by stage (Stage II and Stage III) and mutation type (19Del and L858R) and randomized in a 1:1 ratio to the SYS6010 combined with osimertinib treatment group and the osimertinib monotherapy group. Neoadjuvant therapy will be administered for 3 cycles.

In the surgery stage, the feasibility of surgery will be assessed by a thoracic surgery investigator. Surgery should be performed between Week 10 and Week 12 (i.e., D64-D84 after the first dose of neoadjuvant therapy). Tumor samples collected during surgery will be sent to a central pathology laboratory to assess pathological response.

In the adjuvant therapy stage, all participants who undergo surgery will subsequently enter the adjuvant therapy stage. Participants who do not undergo surgery for reasons other than disease progression will also enter the adjuvant therapy stage.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: +86-0311-69085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able to understand and voluntarily sign the written informed consent form (ICF);
2. Age 18-75 years, regardless of sex;
3. Histologically or cytologically confirmed non-squamous non-small cell lung cancer, staged as resectable or potentially resectable Stage II-IIIB disease according to the International Association for the Study of Lung Cancer (IASLC) 8th Edition TNM staging criteria;
4. Must be eligible for complete surgical resection of the primary tumor;
5. Nodal status must be evaluated by whole-body FDG-PET and contrast-enhanced CT;
6. Confirmed presence of an EGFR-sensitizing mutation (exon 19 deletion or exon 21 L858R mutation, co-mutation with other EGFR sites is allowed), as tested by a central laboratory or local testing facility;
7. No prior systemic anti-tumor therapy (including chemotherapy, biotherapy, targeted therapy, immunotherapy);
8. At least one measurable lesion at baseline as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;
9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1;
10. Life expectancy ≥6 months;
11. Adequate major organ and bone marrow function;
12. Women or men of childbearing potential must use highly effective contraception.

1. Able to understand and voluntarily sign the written informed consent form (ICF); 2. Age 18-75 years, regardless of sex; 3. Histologically or cytologically confirmed non-squamous non-small cell lung cancer, staged as resectable or potentially resectable Stage II-IIIB disease according to the International Association for the Study of Lung Cancer (IASLC) 8th Edition TNM staging criteria; 4. Must be eligible for complete surgical resection of the primary tumor; 5. Nodal status must be evaluated by whole-body FDG-PET and contrast-enhanced CT; 6. Confirmed presence of an EGFR-sensitizing mutation (exon 19 deletion or exon 21 L858R mutation, co-mutation with other EGFR sites is allowed), as tested by a central laboratory or local testing facility; 7. No prior systemic anti-tumor therapy (including chemotherapy, biotherapy, targeted therapy, immunotherapy); 8. At least one measurable lesion at baseline as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; 9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; 10. Life expectancy ≥6 months; 11. Adequate major organ and bone marrow function; 12. Women or men of childbearing potential must use highly effective contraception.

Exclusion Criteria:

1. Diagnosis of Stage I, Stage IIIB with N3, and Stage IIIC, IVA, and IVB non-small cell lung cancer;
2. Multiple primary malignancies (refer to exclusion criterion #8 for synchronous primary lung cancer) OR a mixed histology of SCLC and NSCLC;
3. T4 stage lung cancer due to invasion of the great vessels, carina, trachea, esophagus, heart, or vertebral body; and/or bulky N2 disease;
4. Eligible only for segmentectomy or wedge resection;
5. Receipt of Chinese patent medicine preparations indicated for the treatment of lung cancer within 1 week before randomization;
6. Major surgery or severe traumatic injury within 4 weeks before the first study treatment, or expected to undergo major surgery during the study period;
7. History of other primary malignant tumor (including any known or suspected concurrent primary lung cancer);
8. History of autoimmune disease, immunodeficiency, or organ transplant (except for corneal transplant);
9. Refractory nausea, vomiting, chronic gastrointestinal disease, inability to swallow drugs orally;
10. Evidence of severe or uncontrolled medical conditions (including uncontrolled hypertension, diabetes mellitus, etc,);
11. Active or prior history of interstitial lung disease (ILD)/pneumonitis;
12. Expected to receive live vaccine therapy within 30 days after randomization;
13. History of a definite neurological or mental disorder; known allergy, hypersensitivity, or intolerance to the study drugs or any of their excipients;
14. Pregnant or lactating women;

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: SYS6010 + Osimertinib; Neoadjuvant Therapy: SYS6010 + Osimertinib Adjuvant Therapy: Osimertinib + Pemetrexed + Cisplatin or Carboplatin	Drug: SYS6010; SYS6010 by intravenous (IV) infusion; Drug: Osimertinib; Osimertinib, oral; Other Names: Osimertinib Mesylate Tablets
Active Comparator: Osimertinib; Neoadjuvant Therapy: Osimertinib Adjuvant Therapy: Osimertinib + Pemetrexed + Cisplatin or Carboplatin	Drug: Osimertinib; Osimertinib, oral; Other Names: Osimertinib Mesylate Tablets; Drug: Pemetrexed; 500 mg/m^2 by IV infusion, Q3W; Drug: Cisplatin; 75 mg/m^2 by IV infusion, Q3W; Drug: Carboplatin; AUC 5 mg/mL•min by IV infusion, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) Rate	Defined as the proportion of participants with ≤10% residual viable tumor cells in the resected primary tumor bed, as assessed by blinded independent pathological review (BIPR).	Within 8 weeks post-surgery
Pathological Complete Response (pCR) Rate	The proportion of participants with no residual viable tumor cells in both the resected primary tumor bed and lymph nodes, as assessed by BIPR.	Within 8 weeks post-surgery
Downstaging from N2 to N0/N1 or N1 to N0 at the time of surgery		Within 8 weeks post-surgery
Disease-Free Survival (DFS)	Investigator-assessed DFS per RECIST v1.1	Up to approximately 5.5 years after the last participant enrolled
Event-Free Survival (EFS)	Investigator-assessed DFS per RECIST v1.1	Up to approximately 5.5 years after the last participant enrolled
Objective Response Rate (ORR)	Investigator-assessed ORR per RECIST v1.1	Up to approximately 5.5 years after the last participant enrolled
Overall Survival (OS)		Up to approximately 5.5 years after the last participant enrolled
Incidence of Adverse Events (AEs)		Up to approximately 5.5 years after the last participant enrolled
Anti-drug Antibodies (ADAs) to SYS6010		Up to approximately 5.5 years after the last participant enrolled

Collaborators and Investigators

• Sponsor: CSPC Megalith Biopharmaceutical Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): June 30, 2032

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Estimated): December 1, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 30, 2025
• Last Verified: November 1, 2025

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; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Platinum Compounds; Pemetrexed; Carboplatin; Cisplatin; osimertinib
• Other Study ID Numbers: SYS6010-013

Drug and device information, study documents

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