SCTB14 as first-line therapy for advanced NSCLC

A Phase III, Randomized, Double-blind, Multicenter Clinical Study to Evaluate the Efficacy and Safety of SCTB14 Versus Pembrolizumab as First-Line Therapy in Patients With Driver Gene-Negative, TPS ≥10% Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This trial will test whether SCTB14 works better than pembrolizumab as first treatment for adults with unresectable locally advanced or metastatic, driver-gene–negative NSCLC whose tumors have PD-L1 TPS ≥10%.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 246 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sinocelltech Ltd. (Industry-sponsored)
• Drugs / interventions: immunotherapy, pembrolizumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07362459 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind Phase III trial compares SCTB14 to pembrolizumab as first-line therapy in adults with unresectable locally advanced or metastatic NSCLC who are driver gene–negative and have PD-L1 tumor proportion score (TPS) ≥10%. Enrolled patients with ECOG performance status 0–1 and no prior systemic treatment are randomized to receive SCTB14 or pembrolizumab and followed for tumor response and progression using RECIST criteria. The primary endpoint is progression-free survival with secondary monitoring of overall survival and detailed safety monitoring, including immune-related adverse events. The trial is conducted at Shanghai Chest Hospital and requires tumor tissue for PD-L1 testing and confirmation of EGFR/ALK negativity where applicable.

Who should consider this trial

Good fit: Adults (≥18) with unresectable locally advanced or metastatic NSCLC, ECOG 0–1, no prior systemic therapy, no EGFR sensitizing mutations or ALK rearrangements where required, and a PD-L1 TPS ≥10% are the intended participants.

Not a fit: Patients with EGFR or ALK driver mutations, PD-L1 TPS below 10%, prior systemic anti-tumor therapy for this disease, or poor performance status are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, SCTB14 could extend progression-free survival and provide an alternative first-line option for PD-L1–positive, driver-negative advanced NSCLC patients.

How similar studies have performed: Existing PD-1/PD-L1 drugs such as pembrolizumab have demonstrated first-line benefit in PD-L1–positive NSCLC, while SCTB14 is an investigational agent that has not yet shown phase III results.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign the written informed consent form prior to screening.
2. Age ≥ 18 years, both male and female.
3. ECOG Performance Status score of 0 to 1.
4. An expected survival of ≥ 3 months.
5. Histologically or cytologically confirmed, unresectable locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) Non-Small Cell Lung Cancer (NSCLC) that is not amenable to curative surgery or radical concurrent/sequential chemoradiotherapy.
6. For subjects with non-squamous cell carcinoma, as well as non-smoking subjects with squamous cell carcinoma containing mixed adenocarcinoma components, confirmation of the absence of EGFR sensitizing mutations or ALK gene rearrangements from tumor tissue is required prior to enrollment.
7. Subjects must provide a histology sample suitable for PD-L1 testing, with a Tumor Proportion Score (TPS) ≥ 10%.
8. No prior systemic anti-tumor therapy for the studied disease.
9. At least one measurable non-CNS lesion according to RECIST v1.1 criteria.
10. Adequate function of major organs.

Exclusion Criteria:

1. Known actionable driver gene mutations such as ROS1 fusion, BRAF V600E mutation, NTRK fusion, MET exon 14 skipping mutation, and RET fusion mutation.
2. Received non-specific immunomodulatory therapy or immunosuppressive drugs within 2 weeks before the first dose; received traditional Chinese medicine with antineoplastic indications within 1 week before the first dose.
3. Prior thoracic radiotherapy; or local anti-tumor therapy within 2 weeks before first dosing.
4. Prior treatment with antitumor immunotherapy, antiangiogenic therapy, or other small molecule tyrosine kinase inhibitor (TKI)-based antitumor drugs.
5. subjects with metastasis or compression involving the brainstem, meninges, or spinal cord, or those with active CNS metastases or multiple brain metastases.
6. Imaging demonstrates tumor invasion of major blood vessels, significant necrosis or cavitation within the primary tumor lesions, or the presence of lymphangitic carcinomatosis.
7. Imaging demonstrates tumor invasion or compression of adjacent vital organs or carries a risk of developing an esophagotracheal fistula or esophagopleural fistula.
8. History of hypertensive crisis or hypertensive encephalopathy, or the presence of uncontrolled hypertension despite medication, or poorly controlled diabetes despite pharmacotherapy.
9. A history of arterial thrombosis, deep vein thrombosis, cerebral infarction, transient ischemic attack, or significant vascular disease within 6 months prior to enrollment.
10. A history of myocardial infarction, unstable angina, cardiac insufficiency with New York Heart Association (NYHA) class ≥ III, or severe arrhythmia uncontrolled by medication within 6 months prior to enrollment.
11. The presence of any active autoimmune disease or a history of autoimmune disease with an anticipated recurrence.
12. A history of esophageal/gastric varices, severe ulcer, abdominal fistula, intra-abdominal abscess, gastrointestinal perforation and/or fistula, acute gastrointestinal bleeding, intestinal obstruction, or extensive intestinal resection within 6 months prior to the first dose.
13. A history of bleeding tendency, high bleeding risk, or coagulation dysfunction,.
14. The presence of other malignant tumors.
15. Toxicities from prior neoadjuvant/adjuvant therapy, surgery, radiotherapy, or other previous antitumor treatments have not recovered to Grade 0-1.
16. Receipt of a live or attenuated vaccine within 4 weeks prior to the first dose, or a plan to receive a live or attenuated vaccine during the study period; however, the use of inactivated vaccines is permitted.
17. Presence of any of the following infectious conditions: a) severe infection within 4 weeks prior to the first dose; b) active infection within 2 weeks prior to enrollment; c) active tuberculosis; d) positive HIV antibody; e) active hepatitis B or C; f) known active syphilis.
18. Major surgery planned or anticipated during the study period, or unhealed tissue present before enrollment..
19. Presence of symptomatic or recurrent pleural effusion, pericardial effusion, or ascites requiring drainage.
20. A history of non-infectious pneumonia requiring treatment or the presence of interstitial lung disease
21. A history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
22. Known hypersensitivity to any component of the investigational drug or a documented history of severe hypersensitivity reactions to any other monoclonal antibody.
23. Current participation in another clinical trial, with the exception of observational (non-interventional) studies or the follow-up phase of an interventional trial.
24. Pregnancy or lactation in female subjects.
25. A known history of alcohol or drug addiction, psychiatric disorders, or drug abuse in the subject.
26. Tumor-induced conditions or symptoms associated with a high medical risk.
27. Any other condition deemed by the investigator to be inappropriate for enrollment.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Conditions Non-Small Cell Lung Carcinoma