Overview

This is a multicenter Phase II/III study evaluating the efficacy and safety of SCTB41 combined with chemotherapy versus tislelizumab combined with chemotherapy as first-line treatment in patients with driver-negative locally advanced or metastatic non-small cell lung cancer (NSCLC).

The Phase II portion is an open-label safety run-in study enrolling approximately 30-60 patients to evaluate the safety and tolerability of SCTB41 plus chemotherapy. Following confirmation of acceptable safety and preliminary efficacy, the study will proceed to the Phase III portion.

The Phase III portion is a randomized, double-blind, active-controlled study enrolling approximately 350 patients. Eligible participants will be randomized in a 1:1 ratio to receive SCTB41 plus chemotherapy or tislelizumab plus chemotherapy. The primary objective is to compare progression-free survival assessed by blinded independent central review according to RECIST version 1.1.

Eligibility

Inclusion Criteria:

1. Voluntary written informed consent (ICF) signed prior to screening.
2. Age ≥18 years, male or female.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4. Expected survival ≥3 months.
5. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) that is not amenable to complete surgical resection and is not suitable for definitive concurrent or sequential chemoradiotherapy, according to the 9th edition of the TNM staging system by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC).
6. For subjects with adenocarcinoma, non-smokers, or squamous cell carcinoma with mixed adenocarcinoma components, absence of sensitizing EGFR mutations (e.g., exon 19 deletion, exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I) or ALK gene rearrangements must be confirmed by tumor tissue, cytology, or blood samples prior to enrollment.
7. Availability of tumor tissue samples for PD-L1 testing.
8. No prior systemic anticancer therapy for the study disease.
9. At least one measurable lesion (excluding brain lesions) per RECIST v1.1. 10 Adequate organ function.

Exclusion Criteria:

1. Known ROS1 fusion-positive, BRAF V600E mutation, or other driver mutations for which guideline-recommended first-line targeted therapies are available.
2. Prior thoracic radiotherapy.
3. Symptomatic central nervous system metastases.
4. Imaging evidence during screening showing tumor invasion of major blood vessels, invasion of critical surrounding organs, or risk of tracheoesophageal fistula or esophagopleural fistula as assessed by the investigator.
5. History of hypertensive crisis or hypertensive encephalopathy, or uncontrolled hypertension despite medication.
6. Active autoimmune disease or a history of autoimmune disease with a risk of recurrence.
7. Bleeding tendency, high bleeding risk, or coagulation disorders.
8. Other malignancies.
9. Active serious infection prior to first dose, including active infection, active tuberculosis, HIV positivity, active hepatitis B or C, or known active syphilis.
10. Clinically significant pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
11. History of non-infectious pneumonia requiring systemic corticosteroid therapy or current interstitial lung disease.
12. Prior allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
13. Known allergy to any component of the investigational drug(s), or history of severe hypersensitivity reaction to any monoclonal antibody.
14. Participation in another clinical trial, except for follow-up in observational (non-interventional) studies or follow-up phases of interventional studies.
15. Pregnant or breastfeeding women.
16. Known alcohol or drug abuse, psychiatric disorders, or history of illicit drug use.
17. Any other condition deemed unsuitable for enrollment by the investigator.