SYHX2011 in Combination With Carboplatin and Enlonstobart as First-Line Therapy for Squamous Non-Small Cell Lung Cancer

SYHX2011 in Combination With Carboplatin and Enlonstobart Versus Nab-Paclitaxel Plus Carboplatin and Tislelizumab as First-Line Therapy for Squamous Non-Small Cell Lung Cancer: A Multicenter, Open-Label, Phase II/III Study

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

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: SYHX2011; Drug: Carboplatin; Drug: Enlonstobart; Drug: Nab-Paclitaxel; Drug: Tislelizumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 396
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYHX2011+Carboplatin+Enlonstobart; SYHX2011+Carboplatin+Enlonstobart, One cycle every 3 weeks for 4~6 cycles. Maintenance therapy consists of SYHX2011 (administered every 6 weeks) and Enlonstobart (administered every 3 weeks), with a maximum duration of 2 years, or until disease progression, intolerable toxicity, or withdrawal of informed consent by the patient, whichever occurs first.	Drug: SYHX2011; SYHX2011:260 mg/m^2, IV/30 ± 3 minutes(day1); Other Names: Paclitaxel for Injection(Albumin Bound)(II); Drug: Carboplatin; Carboplatin: AUC 5 mg/mL/min, IV/30~60 minutes(day1); Drug: Enlonstobart; Enlonstobart: 360 mg, IV/60 minutes(day1); Other Names: SG001
Active Comparator: Nab-Paclitaxel +Carboplatin+Tislelizumab; Nab-Paclitaxel +Carboplatin+Tislelizumab,One cycle every 3 weeks for 4~6 cycles. Maintenance therapy consists of Nab-Paclitaxel (administered every 6 weeks) and Tislelizumab (administered every 3 weeks), with a maximum duration of 2 years, or until disease progression, intolerable toxicity, or withdrawal of informed consent by the patient, whichever occurs first.	Drug: Carboplatin; Carboplatin: AUC 5 mg/mL/min, IV/30~60 minutes(day1); Drug: Nab-Paclitaxel; Nab-Paclitaxel: 260 mg/m^2, IV/30 ± 3 minutes(day1); Other Names: Albumin-bound Paclitaxel; Drug: Tislelizumab; Tislelizumab: 200 mg, IV/60 minutes(day1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) for phase II	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.	Throughout the study period, an average of 3 years
Progression Free Survival (PFS) for phase III	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.	Throughout the study period, an average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity(DLT) only assessed in the safety run-in cohort	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.	From the first dose finished to 21 days
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment	To identify the incidence and the type of AEs, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams.	From the first dose finished to 28 days after the last dose
ORR(iRECIST)	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.	Throughout the study period, an average of 3 years
Disease Control Rate(DCR)	The proportion of patients achieving complete response (CR), partial response (PR), and stable disease (SD) among all patients over the entire study period.	Throughout the study period, an average of 3 years
Duration of Response (DoR)	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.	Throughout the study period, an average of 3 years
Overall Survival	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.	Throughout the study period, an average of 5 years

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Squamous Non-small Cell Lung Cancer; Enlonstobart; First-Line Therapy; SYHX2011
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Albumins; Albumin-Bound Paclitaxel; Carboplatin; Paclitaxel; 130-nm albumin-bound paclitaxel; tislelizumab
• Other Study ID Numbers: CSPC-XBZ-LUNG-K01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No