Non-Small Cell Lung Cancer
Conditions
Keywords
SYHX2011, Enlonstobart, Squamous Non-small Cell Lung Cancer, First-Line Therapy
Brief summary
Efficacy and Safety of SYHX2011 Combined with Carboplatin and Enlonstobart versus Nab-Paclitaxel Combined with Carboplatin and Tislelizumab as First-Line Treatment for Squamous Non-Small Cell Lung Cancer
Detailed description
This is a multicenter, open-Label, phase II/III study in patients with squamous non-small cell lung cancer. Phase II will adopt a single-arm study design. The first 12 enrolled patients will be designated as the safety run-in cohort. Upon completion of safety observation after the first dose administration, the recommended dose will be selected for the expansion phase based on the safety and efficacy outcomes of the safety run-in phase.If the Phase II study results demonstrate that the combination therapy at the recommended dose is tolerable and has a favorable safety profile in trial participants, with preliminary evidence of anti-tumor activity, the investigators will determine whether to initiate the Phase III study. The current guideline-recommended first-line treatment regimen is planned to be selected as the control arm, and a randomized, controlled, open-label study design will be adopted. Participants will receive the study regimen (experimental arm) or the control regimen in accordance with the randomization results.
Interventions
DRUGSYHX2011
SYHX2011:260 mg/m\^2, IV/30 ± 3 minutes(day1)
DRUGCarboplatin
Carboplatin: AUC 5 mg/mL/min, IV/30\~60 minutes(day1)
DRUGEnlonstobart
Enlonstobart: 360 mg, IV/60 minutes(day1)
DRUGNab-Paclitaxel
Nab-Paclitaxel: 260 mg/m\^2, IV/30 ± 3 minutes(day1)
DRUGTislelizumab
Tislelizumab: 200 mg, IV/60 minutes(day1)
Sponsors
Shanghai Chest Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age: ≥18 years old 2. Histologically or cytologically confirmed locally advanced or metastatic squamous non-small cell lung cancer (Stage IIIB, IIIC, or IV according to the IASLC 9th Edition TNM Staging System), ineligible for radical surgery and/or radical radiotherapy 3. Confirmed negative for driver genes (including EGFR mutation, ALK fusion, ROS1 fusion, etc.) 4. Tumor cell PD-L1 expression in tumor tissue ≥1% (TPS ≥1%) 5. No prior systemic anti-tumor therapy for Stage IIIB/IIIC and IV NSCLC, including chemotherapy, targeted therapy, biological therapy, immunotherapy, immunomodulatory drugs, Chinese herbal medicines or proprietary Chinese medicines, and other investigational drugs for tumor control 6. ECOG PS score 0\~1 7. At least one measurable lesion according to the RECIST 1.1 criteria 8. Adequate bone marrow and other organ functions:(1)Hematology: No significant signs of hematological disease; absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count (PLT) ≥75×10\^9/L, hemoglobin (Hb) ≥90 g/L at screening. For patients with hematological indicators at the critical value who fail to meet the above criteria, the investigator will determine eligibility based on the patient's physical condition. (2)Coagulation function: International Normalized Ratio (INR) ≤1.5 × upper limit of normal (ULN); activated partial thromboplastin time (APTT) ≤1.5 × ULN. (3)Hepatic and renal function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≤2.5 × ULN; for patients with hepatic metastasis, both AST and ALT ≤5 × ULN. Total bilirubin (TBiL) ≤1.5 × ULN; for patients with known Gilbert's disease: serum total bilirubin level ≤3 × ULN. Serum creatinine (Cr) ≤1.5 × ULN 9. Expected survival ≥3 months 10. Able to understand the study details; the patient and/or legal guardian voluntarily consents to participate in the study and signs the informed consent form
Exclusion criteria
1. History of or current with other malignant tumors (excluding non-melanoma skin cancer, in situ breast cancer, in situ cervical cancer, and superficial bladder cancer that have been effectively controlled within the past 5 years) 2. Active leptomeningeal disease or poorly controlled, untreated brain metastases (excluding patients with brain metastases that are well-controlled with local therapy) 3. Interstitial lung disease (ILD), drug-induced interstitial pneumonitis, or non-infectious pneumonitis (including radiation pneumonitis, pulmonary fibrosis, acute lung disease requiring steroid therapy), and patients with severe impairment of pulmonary function 4. Active autoimmune disease or a history of autoimmune disease (e.g., ulcerative colitis, Crohn's disease, etc.). However, participants with the following conditions are eligible for further screening: well-controlled type 1 diabetes mellitus; well-controlled hypothyroidism requiring only hormone replacement therapy; dermatological diseases not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia); or participants with diseases not expected to relapse in the absence of external triggers 5. Peripheral neuropathy of Grade ≥2 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 6.0 6. Pleural effusion, peritoneal effusion, or pericardial effusion requiring clinical intervention within 2 weeks prior to the first administration of the study drug 7. History of severe cardiovascular disease within 6 months prior to the first administration of the study drug, including but not limited to:(1)Severe cardiac rhythm or conduction abnormalities (e.g., ventricular arrhythmias requiring clinical intervention, third-degree atrioventricular block, etc.); Fridericia-corrected QT interval (QTcF) \> 480 ms (Fridericia formula: QTcF=QT/RR\^0.33, where RR=60/heart rate);(2)History of myocardial infarction, unstable angina pectoris, angioplasty, or coronary artery bypass graft surgery;(3)Heart failure of New York Heart Association (NYHA) Functional Class Ⅱ or higher; left ventricular ejection fraction (LVEF) \< 50% as detected during screening 8. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: Hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (anti-HBc) positive, with HBV DNA copy number ≥ 1×10\^4 copies/mL (or ≥ 2000 IU/mL); Hepatitis C virus antibody (anti-HCV) positive, with HCV RNA level exceeding the lower limit of quantification (LLOQ) of the applied analytical method 9. Severe infection occurring within 4 weeks prior to the first study drug administration (including but not limited to bacteremia requiring hospitalization, severe pneumonia, active pulmonary tuberculosis, etc.); active infection requiring systemic antibiotic therapy within 2 weeks prior to the first study drug administration 10. Lactating or pregnant females; females of childbearing potential with a positive blood pregnancy test within 7 days before study enrollment; all male and female patients of childbearing potential who decline to use highly effective contraceptive methods throughout the study period and for 6 months after the last drug administration 11. Known hypersensitivity or anaphylaxis to any study drug, or a history of other severe hypersensitivity reactions 12. History of immunodeficiency (including positive human immunodeficiency virus (HIV) test results, other acquired or congenital immunodeficiency diseases); a history of allogeneic stem cell or organ transplantation; other conditions that the investigator deems unsuitable for study participation (e.g., psychiatric disorders, uncontrolled or poorly controlled hypertension and diabetes mellitus, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) for phase II | Throughout the study period, an average of 3 years | Objective response rate (ORR) is assessed by the investigator analysis of tumor growth through imaging follow-up (CT scan/MRI), using a method to evaluate it as RECIST V1.1. This will be considered as the number of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the period of treatment with SYHX2011. Tumor measurements that were assessed locally by the clinician according to RECIST, V1.1, should be recorded and indicate the change in size of tumors as compared with baseline, at the first dose of study treatment. |
| Progression Free Survival (PFS) for phase III | Throughout the study period, an average of 3 years | Progression free survival (PFS): Time from first dosing date to the date of confirmed PD according to RECIST 1.1. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity(DLT) only assessed in the safety run-in cohort | From the first dose finished to 21 days | Adverse events (including signs, symptoms, diseases, and clinically significant abnormal laboratory test values) related to the study drug (with causal relationships categorized as definite, probable, or possible) occurring during the DLT observation period. |
| Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | From the first dose finished to 28 days after the last dose | To identify the incidence and the type of AEs, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams. |
| ORR(iRECIST) | Throughout the study period, an average of 3 years | Objective response rate (ORR) is assessed by the investigator analysis of tumor growth through imaging follow-up (CT scan/MRI), using a method to evaluate it as iRECIST. |
| Disease Control Rate(DCR) | Throughout the study period, an average of 3 years | The proportion of patients achieving complete response (CR), partial response (PR), and stable disease (SD) among all patients over the entire study period. |
| Duration of Response (DoR) | Throughout the study period, an average of 3 years | Duration of response (DoR): is defined as the time from first confirmed response (complete (CR) or partial (PR) response), to the date of the documented progression of the disease (PD) as determined using RECIST V1.1 criteria or death due to any cause, whichever occurs first. Those patients with response and without PD or death event will be censored on the date of their last tumor assessment. |
| Overall Survival | Throughout the study period, an average of 5 years | Overall survival was defined as the time interval (in days) from the randomization date to the date of death. If a participant was still alive at the end of the study or was lost to follow-up, survival time was censored at their last contact date or the end of the study date, whichever was first. |
Outcome results
None listed