SYS6010 Combined With Enlonstobart Versus Immunotherapy+ Platinum-based Chemotherapy for Patients With PD-L1-Positive Locally Advanced or Metastatic NSCLC（SYNSTAR 04）

Official title

An Open-label, Multicenter Randomized Phase III Study of SYS6010 Combined With Enlonstobart Versus Immunotherapy+ Platinum-based Chemotherapy as First-Line Treatment for Patients With PD-L1-Positive Locally Advanced or Metastatic NSCLC

Overview

This study was an open-label, multi-center, randomized phase III study to evaluate the efficacy and safety of SYS6010 combined with Enlonstobart versus Immunotherapy+ Platinum-based chemotherapy as First-Line treatment for patients with PD-L1-Positive locally advanced or metastatic NSCLC.

Detailed description

Avoid duplicating information that will be entered elsewhere, such as Eligibility Criteria or Outcome Measures.

Interventions

• Drug SYS6010 injection
  SYS6010 is Lyophilized powder for injection as an EGFR-ADC. SYS6010 will be administered via intravenous infusion, Q3W, with 21 days as one treatment cycle, at a dose of 4.5 mg/kg.
• Drug Enlonstobart injection
  Enlonstobart is arecombinant human anti-PD-1 monoclonal antibody injection，and will be administered by intravenous infusion, Q3W, with 21 days as one treatment cycle at a dosage of 360 mg.
• Drug Tislelizumab injection
  Tislelizumab is a marketed recombinant human anti-PD-1 monoclonal antibody injection, and will be administered by intravenous infusion, Q3W, with 21 days as one treatment cycle at a dosage of 200 mg.
• Drug Paclitaxel+Carboplatin or Pemetrexed + Cisplatin/Carboplatin
  Paclitaxel+Carboplatin or Pemetrexed + Cisplatin/Carboplatin are widely accepted and common chemotherapy medication. For squamous NSCLC, Paclitaxel+Carboplatin were recommended to be administrated on a 21-day cycle. For nonsquamous NSCLC, Pemetrexed + Cisplatin or Carboplatin were recommended to be administrated on a 21-day cycle.

Primary outcome measures

• Progression Free Survival (PFS) assessed by IRC [Time frame: 2 years]

Secondary outcome measures (12)

• Overall survival (OS) [Time frame: 2 years]
• ORR assessed by investigators and IRC [Time frame: 1.5years]
• DoR assessed by investigators and IRC [Time frame: 1.5years]
• The Proportion of ADAanti-drug antibody positive of SYS6010 and Enlonstobart [Time frame: 1.5years]
• The severity and frequency of Adverse Event (AE)and Serious Adverse Event (SAE) assessed by CTCAE v6.0. [Time frame: 2 years]
• Tmax of SYS6010 and Enlonstobart [Time frame: 1.5 years]
• The Scale of Quality of Life assessed by participants [Time frame: 2 years]
• Cmax of SYS6010 and Enlonstobart [Time frame: 1.5 years]
• AUC0-504h of SYS6010 and Enlonstobart [Time frame: 1.5 years]
• t1/2 of SYS6010 and Enlonstobart [Time frame: 1.5 years]
• CL of SYS6010 and Enlonstobart [Time frame: 1.5 years]
• Vz of SYS6010 and Enlonstobart [Time frame: 1.5 years]

Eligibility criteria

Inclusion criteria

• Aged 18-75 (inclusive) years old, male or females;
• Participants with pathologically confirmed locally advanced or metastatic NSCLC. Including participants with stage IIIB or IIIC according to the 9th edition of AJCC staging who are not suitable for surgical resection or radical chemoradiotherapy, or participants with stage IV NSCLC
• Participants who have not previously received systemic anti-tumor treatment. Those who have previously received adjuvant/neoadjuvant therapy will be allowed for inclusion if disease progression occurs 12 months after the end of treatment.
• EGFR mutation negative and ALK fusion negative
• Participants with PD-L1 TPS≥1% according to centralized laboratory test
• At least one measurable lesion confirmed by CT or MRI scan according to RECIST v1.1 criteria
• ECOG performance status of 0-1;
• Life expectancy ≥ 3 months;
• Major organ function must meet the criteria within 7 days prior to the first dose of the study intervention
• 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;
• Voluntarily participate in this clinical study, understand the study procedures, and be able to sign a written informed consent form.

Exclusion criteria

• Histology or cytology of the tumor confirms the presence of combined small cell lung cancer, neuroendocrine carcinoma, or sarcomatoid carcinoma;
• Participants with ROS1/RET/NTRK fusions, MET exon 14 skipping mutation, or BRAF V600E mutation.
• Participants 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;
• Participants 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.;
• Participants who are known to be allergic to any component of SYS6010, Enlonstobart, Tislelizumab or to humanized monoclonal antibody products or ; Paclitaxel/Carboplatin/ Pemetrexed/Cisplatin.
• Previously treated with topoisomerase I inhibitor toxin ADC therapy
• AEs caused by prior anti-tumor treatment have not recovered to ≤ Grade 1 (excluding Grade 2 alopecia and other toxicities judged by the investigator to have no safety risk) according to NCI-CTCAE v6.0; Participants who experienced ≥ grade 3 irAEs during previous treatment, or who permanently discontinued medication due to irAEs
• Patients who have not met the corresponding washout period requirements for the medications or treatments should be excluded；
• History of severe cardiovascular or cerebrovascular disease within 6 months prior to the first dose of the study intervention\\
• 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;
• 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;
• Participants with active autoimmune diseases or a history of autoimmune diseases (such as ulcerative colitis or Crohn's disease) are excluded, but participants with the following conditions are allowed to proceed to further enrollment screening: well-controlled type 1 diabetes and hypothyroidism that is well-controlled with only hormone replacement therapy.
• Pleural effusion or pericardial effusion requiring clinical intervention within 2 weeks prior to the first dose;
• Active HBV or HCV infection (hepatitis B surface antigen and/or hepatitis B core antibody positive and HBV DNA copies ≥ 1×10\^4 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;
• History of immunodeficiency (including positive HIV test, other acquired or congenital immunodeficiency diseases), history of allogeneic stem cell or organ transplant;
• Other conditions that the investigator deem unsuitable for participation in this clinical study. Such as mental illness, uncontrolled or poorly controlled hypertension (defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥95 mmHg after standardized antihypertensive treatment), and diabetes, etc.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07633873 · SYS6010-022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗