A Study of SYS6010 and Platinum-based Chemotherapy in Patients With EGFR-mutated NSCLC.

Phase 3

Not yet recruiting

• Conditions: EGFR-mutated Locally Advanced or Metastatic NSCLC
• Interventions: Drug: SYS6010; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

• Registration Number: NCT06927986
• Lead Sponsor: CSPC Megalith Biopharmaceutical Co.,Ltd.

Brief Summary

To evaluate the efficacy and safety of SYS6010 versus platinum-based chemotherapy in participants with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)

Detailed Description

This is a randomized, open-label, multi-center, phase III clinical study, aiming to evaluate the efficacy and safety of SYS6010 versus platinum-based chemotherapy in participants with EGFR-mutated locally advanced or metastatic NSCLC who have failed EGFR TKI therapy.

Study Timeline

• Study First Submitted: 2025-03-12
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-07
• Last Update Submitted: 2025-04-07
• Study First Posted: 2025-04-15
• Last Update Posted: 2025-04-15
• Study Start: 2025-04-30
• Primary Completion: 2026-07-30
• Study Completion: 2026-08-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

• 1. Aged 18-75 (inclusive) years old, male or females;
• 2. Patients with histologically confirmed locally advanced or metastatic NSCLC, including those in stage IIIB or IIIC based on 8th edition of the AJCC staging system who are not suitable for surgical resection or radical chemoradiotherapy, or those with stage IV NSCLC. Patients with EGFR-mutated locally advanced or metastatic NSCLC who have failed EGFR TKI therapy targeting locally advanced or metastatic disease (third-generation marketed EGFR TKI must be included);
• 3. Presence of at least one EGFR-sensitive mutation;
• 4. At least one measurable lesion confirmed by CT or MRI scan according to RECIST v1.1 criteria;
• 5. ECOG performance status of 0-1;
• 6. Life expectancy ≥ 3 months;
• 7. Major organ function must meet the following criteria within 7 days prior to the first dose of the study intervention (No component transfusion, G-CSF, TPO, IL-11, or EPO within 2 weeks prior to the first dose): Hematology： Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥100×10^9/L; Hemoglobin (HGB) ≥100g/L. Renal function Cr：≤ 1.5 × upper limit of normal (ULN) and creatinine clearance ≥ 50 mL/min; Liver function Serum total bilirubin (TBIL) ：≤ 1.5 × ULN, ≤ 3 × ULN for patients with Gilbert syndrome/metastases to liver Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)：≤ 2.5 × ULN, ≤ 5 × ULN for patients with metastases to liver Coagulation function Coagulation function Activated partial thromboplastin time (APTT) and international normalised ratio (INR)： ≤1.5×ULN
• 8. Women of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first dose. Participants must agree to use effective contraception from the time of signing the informed consent form until 7 months after the last dose; during this period, women should not be breastfeeding, and men should avoid donating sperm;
• 9. Voluntarily participate in this clinical study, understand the study procedures, and be able to sign a written informed consent form.

Exclusion Criteria

• 1. Histologically or cytologically confirmed combined small cell lung cancer, neuroendocrine carcinoma,or carcinosarcoma
• 2. Patients with meningeal metastasis, brainstem metastasis, spinal cord metastasis and/or compression, or active CNS metastasis. Patients with supratentorial and/or cerebellar metastasis (i.e., without mesencephalon, pons, or medulla involvement) who have received local treatment, have achieved stability for at least 2 weeks prior to the first dose of the study intervention (imaging shows no new brain metastasis or enlargement of existing brain metastasis, and all neurologic symptoms have stabilized or returned to normal), and do not require corticosteroid therapy or are receiving prednisone at a daily dose of ≤10 mg or equivalent doses of other corticosteroids, can participate in the study;
• 3. Patients with a history of other malignant tumors within 3 years prior to the first dose of the study intervention, except for the following conditions: cured skin basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, and cervical carcinoma in situ, etc.;
• 4. Patients who are known to be allergic to any component of SYS6010 or to humanized monoclonal antibody products; allergic to carboplatin, cisplatin, or pemetrexed, or have contraindications for their use;
• 5. AEs caused by prior anti-tumor treatment have not recovered to ≤ Grade 1 (excluding Grade 2 alopecia, peripheral neurotoxicity, and other toxicities judged by the investigator to have no safety risk) according to NCI-CTCAE v5.0;
• 6. Previously received systemic anti-tumor therapy for locally advanced or metastatic non-squamous NSCLC other than EGFR TKI; patients who have previously received adjuvant/neoadjuvant chemotherapy and experienced disease progression more than 12 months after the end of treatment are allowed to be included;

• 7. Patients who have not met the corresponding washout period requirements for the following medications or treatments should be excluded:

  8. Major surgery (excluding needle biopsy)：At least 4 weeks

  9. Chemotherapy, radical radiotherapy, targeted therapy, endocrine therapy, immunotherapy：At least 4 weeks

  10. Oral fluorouracils, small molecule targeted drugs, traditional Chinese medicines with anti-tumor indications, palliative radiation or local therapy：At least 2 weeks

  11. Glucocorticoids (prednisone >10 mg/day or equivalent dose of similar drugs),intravenous injection of antibiotics, antifungals, or antivirals：At least 2 weeks

  12. Investigational product and Live attenuated vaccine：At least 4 weeks

  13. Strong CYP3A4 inducers or inhibitors, OATP1B1 and OATP1B3 inhibitors：At least 2 weeks

• 8. History of severe cardiovascular or cerebrovascular disease within 6 months prior to the first dose of the study intervention, including but not limited to:

  9. Presence of severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, third-degree atrioventricular block, Fridericia-corrected QT interval > 470 ms (Fridericia formula: QTcF = QT/RR0.33, RR = 60/heart rate);

  10. History of myocardial infarction, unstable angina pectoris, aortic dissection, angioplasty, or coronary artery bypass;

  11. NYHA class II or higher cardiac failure, LVEF<50% at screening;

  12. Stroke or other Grade 3 or higher cardiovascular and cerebrovascular events;

  13. Pulmonary embolism;

• 9. Imaging examination suggests tumor invasion of the cervical, thoracic, and abdominal great vessels;
• 10. Patients who have a history of ILD/non-infectious pneumonitis treated with corticosteroids in the past, currently have ILD/non-infectious pneumonitis, for whom imaging examinations at screening cannot rule out ILD/non-infectious pneumonitis, or whose pulmonary function test indicates severe ventilatory dysfunction and/or decreased diffusion capacity;
• 11. Presence of severe infections within 4 weeks prior to the first dose of the study intervention, including but not limited to bacteraemia requiring hospitalisation, severe pneumonia, active pulmonary tuberculosis infection, etc.; presence of active infections requiring systemic antibiotics within 2 weeks prior to the first dose of the study intervention;
• 12. Previous interruption of EGFR-targeted therapy for ≥1 month or permanent discontinuation due to skin toxicity, or currently have skin diseases requiring oral or intravenous medication;
• 13. History of ulcerative colitis or Crohn's disease;
• 14. Pleural effusion or pericardial effusion requiring clinical intervention within 2 weeks prior to the first dose;
• 15. Active HBV or HCV infection (hepatitis B surface antigen and/or hepatitis B core antibody positive and HBV DNA copies ≥ 1×104 copies/mL or ≥ 2000 IU/mL, HCV antibody positive and HCV RNA above the lower limit of detection of the analytical procedure). Note: For HBsAg-positive patients, it is recommended to start antiviral therapy before the first dose of the study intervention, nucleoside analogues are recommended, such as entecavir, tenofovir disoproxil;
• 16. History of immunodeficiency (including positive HIV test, other acquired or congenital immunodeficiency diseases), history of allogeneic stem cell or organ transplant;
• 17. Other conditions that the investigator deems unsuitable for participation in this clinical study (such as mental disorders, macular cystoid oedema, severe corneal disorders, uncontrolled or poorly controlled hypertension and diabetes mellitus).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SYS6010	SYS6010	-
Platinum-containing chemotherapy	Pemetrexed	Pemetrexed injection 500 mg/m\^2 + cisplatin 75 mg/m\^2 or carboplatin (AUC=5, Calvert formula) administered via intravenous infusion，Q3W
Platinum-containing chemotherapy	Cisplatin	Pemetrexed injection 500 mg/m\^2 + cisplatin 75 mg/m\^2 or carboplatin (AUC=5, Calvert formula) administered via intravenous infusion，Q3W
Platinum-containing chemotherapy	Carboplatin	Pemetrexed injection 500 mg/m\^2 + cisplatin 75 mg/m\^2 or carboplatin (AUC=5, Calvert formula) administered via intravenous infusion，Q3W

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) assessed by independent review committee (IRC)	Up to approximately 1.5 years	Defined as the time from randomisation until the date of objective disease progression or death was assessed by IRC according to RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Investigator-assessed PFS	Up to approximately 1.5 years	Defined as the time from randomisation until the date of objective disease progression or death was assessed by investigator according to RECIST 1.1
Disease Control Rate (DCR)	Up to approximately 2 years	Defined as the percentage of subjects who have a best overall response of CR or PR or SD based on IRC and investigator according to RECIST 1.1
Objective response rate (ORR)	Up to approximately 1.5 years	: Defined as the proportion of patients with response (including CR and PR) assessed by the investigator and the IRC according to RECIST v1.1.
Overall Survival (OS)	Up to approximately 2 years	Defined as the time from randomization until death from any cause
Incidence of adverse events (AEs)	Up to approximately 2 years	AEs graded by CTCAE version 5.0
Serious adverse events (SAEs)	Up to approximately 2 years	SAEs graded by CTCAE version 5.0
EORTC QLQ-LC13 questionnaire	Up to approximately 2 years	EORTC QLQ-LC13 incorporates one multi-item scale to assess dyspnoea, and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and haemoptysis.
EORTC QLQ-30 questionnaire	Up to approximately 2 years	EORTC QLQ-C30 is designed to measure cancer patients' physical, psychological and social functions.
Plasma concentrations of toxin-bound antibodies	Up to approximately 2 years	Tests are conducted after single and continuous administration of SYS6010.
Plasma concentrations of total antibodies	Up to approximately 2 years	Tests are conducted after single and continuous administration of SYS6010.
Plasma concentrations of free toxin (JS-1)	Up to approximately 2 years	Tests are conducted after single and continuous administration of SYS6010.
anti-SYS6010 antibodies (ADA)	Up to approximately 2 years	Incidence of SYS6010 anti-drug antibodies