A Randomized, Open-label, Multicenter, Phase III Clinical Trial to Evaluate the Safety and Efficacy of SYS6010 in Combination With Osimertinib in Patients With EGFR-mutant Locally Advanced or Metastatic Non-small Cell Lung Cancer

Official Summary

This study is a randomized, open-label, multicenter Phase III clinical trial evaluating patients with EGFR-mutant locally advanced or metastatic NSCLC. The Phase III study is planned to enroll approximately 680 participants, who will be randomized in a 1:1 ratio into the following groups: Test group: SYS6010 + osimertinib Control group: Investigator's choice of one treatment（Osimertinib or Osimertinib+ Chemotherapy）

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 75 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 680 participants

Study Arms

• SYS6010 combination (EXPERIMENTAL)
  SYS6010 + Osimertinib
• Investigator's Choice of treatment (ACTIVE_COMPARATOR)
  Investigator's choice of treatment means the treatment chosen by investigators to treat NSCLC including Osimertinib or Osimertinib plus platinum-pemetrexed Osimertin.ib

Interventions

• DRUG: SYS6010 — SYS6010，intravenous injection
• DRUG: Osimertinib — Osimertinib 80mg P.O. QD
• DRUG: platinum-pemetrexed — Pemetrexed (500 mg/m\^2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by pemetrexed maintenance (500 mg/m\^2) every 3 weeks. Pemetrexed (500 mg/m\^2) plus cisplatin (75 mg/m\^2) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by pemetrexed maintenance (500 mg/m\^2) every 3 weeks.

Primary Outcomes

• Progression Free Survival(PFS) evaluated by IRC (Up to 3.5 years)

Secondary Outcomes

• Progression Free Survival(PFS) evaluated by investigator (Up to 2.5 years)
• Overall survival (OS) (Up to 2.5 years)
• Objective Response Rate (ORR) (Up to 2.5 years)
• Duration of Response (DOR) (Up to 2.5 years)
• Disease Control Rate (DCR) (Up to 2.5 years)

Eligibility Criteria

Inclusion Criteria:

1. Age 18 \~ 75 (inclusive) years old, regardless of gender;
2. Patients with pathologically confirmed locally advanced or metastatic NSCLC, including: patients with stage IIIB or IIIC based on AJCC staging version 8 who are not suitable for surgical resection or radical chemoradiotherapy, or patients with stage IV NSCLC. For the dose escalation phase, patients must have EGFR-mutant locally advanced or metastatic NSCLC that has failed previous standard therapy, and for the dose selection phase and phase III study, patients must have EGFR-mutant locally advanced or metastatic NSCLC, which has not received EGFR-TKIs or other systemic therapy before. Patients who have received adjuvant/neoadjuvant chemotherapy may be included if disease progression occurred at least 6 months after completing treatment;
3. Carry at least one EGFR-sensitive mutation (ex19del or L858R, which can be combined with other EGFR mutations). EGFR mutation: Stage Ib: can be enrolled based on previous test results. Phase III: Take the test results of the central laboratory as the admission group;
4. At least one measurable lesion confirmed by CT or MRI, as defined by RECIST v1.1 criteria;
5. ECOG performance status score 0-1;
6. Expected survival ≥ 3 months;
7. Major organ function meets the relevant laboratory test standards for hematology, renal function, liver function, and coagulation within 7 days prior to treatment;
8. Women of childbearing age had a negative blood pregnancy test within 7 days prior to the first use of study drug. Participants must agree to take effective contraceptive measures from signing the informed consent form to 7 months after the last dose, during which women are non-breastfeeding and men avoid sperm donation;
9. Volunteer to participate in this clinical study, understand the study procedures, and be able to sign a written informed consent form.

Exclusion Criteria:

1. Patients with meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active CNS metastases;
2. History of other malignant tumors within 3 years prior to the first use of study drug, except for the following conditions: cured skin basal cell or squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, or cervical carcinoma in situ, etc.;
3. Known allergies to SYS6010 or any ingredient of Osimertinib, or to humanized monoclonal antibodies;
4. Adverse events caused by prior anti-tumor therapy that have not resolved to ≤ Grade 1 (as per NCI-CTCAE v6.0), except for Grade 2 alopecia or peripheral neuropathy deemed by the investigator not to pose a safety risk;
5. Use of any of the medications or treatments within the specified washout period (prior to first dose of study drug)
6. History of serious cardiovascular or cerebrovascular conditions within 6 months prior to the first dose, including but not limited to:Severe arrhythmias (e.g., ventricular arrhythmias requiring clinical intervention, third-degree atrioventricular block, QTcF \> 470 ms) (Fridericia formula: QTcF = QT/RR0.33, RR = 60/heart rate). Myocardial infarction, unstable angina, aortic dissection, angioplasty, or coronary artery bypass surgery. NYHA class II or higher heart failure with LVEF \< 50%.Stroke or other grade ≥ 3 cardiovascular/cerebrovascular events. pulmonary embolism.
7. 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;
8. Severe infection within 4 weeks prior to the first dose, such as bacteremia requiring hospitalization, severe pneumonia, or active pulmonary tuberculosis; Active systemic infections requiring antibiotics within 2 weeks prior to administration;
9. Currently suffering from a skin condition requiring oral or vein administration;
10. Participants with active autoimmune disease or a history of autoimmune disease (e.g., ulcerative colitis or Crohn's disease) are excluded from the study. However, participants with the following conditions may be considered eligible for further screening: those with well-controlled type 1 diabetes, well-controlled hypothyroidism requiring only hormone replacement therapy, skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia), or diseases unlikely to relapse even when exposed to external triggers;
11. Pleural or peritoneal effusion or pericardial effusion requiring clinical intervention;
12. Conditions that seriously affect gastrointestinal absorption as judged by the investigator (such as Persistent nausea, vomiting, chronic gastrointestinal diseases, gastrointestinal surgery, etc.);
13. Active HBV or HCV infection (hepatitis B surface antigen and/or hepatitis B core antibody positive and HBV DNA copy number ≥ 1 × 10

Contact Information

• Clinical Trials Information Group officer — CONTACT
  Phone: 031169085587
  Email: ctr-contact@cspc.cn

More NSCLC Trials

View all NSCLC clinical trials