Non-Small Cell Lung Cancer
Conditions
Brief summary
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.
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.
Interventions
DRUGSYS6010
SYS6010 by intravenous (IV) infusion
DRUGOsimertinib
Osimertinib, oral
DRUGPemetrexed
500 mg/m\^2 by IV infusion, Q3W
DRUGCisplatin
75 mg/m\^2 by IV infusion, Q3W
DRUGCarboplatin
AUC 5 mg/mL•min by IV infusion, Q3W
Sponsors
CSPC Megalith Biopharmaceutical Co.,Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, Open-label, Phase II
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) Rate | Within 8 weeks post-surgery | 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). |
| Pathological Complete Response (pCR) Rate | Within 8 weeks post-surgery | The proportion of participants with no residual viable tumor cells in both the resected primary tumor bed and lymph nodes, as assessed by BIPR. |
| Downstaging from N2 to N0/N1 or N1 to N0 at the time of surgery | Within 8 weeks post-surgery | — |
| Disease-Free Survival (DFS) | Up to approximately 5.5 years after the last participant enrolled | Investigator-assessed DFS per RECIST v1.1 |
| Event-Free Survival (EFS) | Up to approximately 5.5 years after the last participant enrolled | Investigator-assessed DFS per RECIST v1.1 |
| Objective Response Rate (ORR) | Up to approximately 5.5 years after the last participant enrolled | Investigator-assessed ORR per RECIST v1.1 |
| 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 | — |
Contacts
Primary ContactClinical Trials Information Group officer
Outcome results
None listed