SKB264 Plus Glecirasib in Advanced KRAS G12C-Mutant NSCLC: A Phase II Study

NCT07670013 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-1542
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, single-arm, phase II (Simon two-stage) prospective interventional clinical study. The primary objective is to evaluate the efficacy and safety of SKB264 in combination with Glecirasib (a KRAS G12C inhibitor) as first-line treatment in patients with KRAS G12C-mutated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Specifically, the primary endpoint is the objective response rate (ORR) assessed by investigators per RECIST 1.1 to verify the core antitumor activity of the combination regimen. Secondary objectives include comprehensive evaluation of overall efficacy via disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), and overall survival (OS). Safety will be monitored in accordance with NCI CTCAE 5.0, including the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), to characterize the safety profile of the combination and the feasibility of dose modifications. This study aims to provide scientific evidence for the use of this combination regimen as first-line therapy for KRAS G12C-mutated advanced NSCLC and to explore a more optimal treatment option for this patient population.

Conditions

NSCLC

Keywords

SBK264; Goleirex

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate as Assessed by RECIST v1.1

  Objective response rate (ORR) refers to the proportion of patients whose tumors have shrunk to a certain extent and maintained that state for a certain period of time, including cases of complete response (CR) and partial response (PR) as assessed by RECIST v1.1.

  From enrollment to the end of treatment at 12 months

Secondary Outcomes (1)

• Progression-free Survival as Assessed by RECIST v1.1

  From enrollment to the end of treatment at 12 months

Study Arms (1)

SKB264 + Goleirex

EXPERIMENTAL

Patients with KRAS G12C-mutated advanced non-squamous non-small cell lung cancer (NSCLC) receive first-line treatment with SKB264 in combination with Glecirasib (a KRAS G12C inhibitor). The therapeutic efficacy and safety of this combination regimen will be evaluated throughout the study.

Drug: SKB264; Drug: Goleirex

Interventions

SKB264 DRUG

4 mg/kg intravenously every 2 weeks

SKB264 + Goleirex

Goleirex DRUG

600 mg orally once daily

SKB264 + Goleirex

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the study and sign the informed consent form (ICF).
• Male or female subjects aged ≥18 years and ≤75 years at the time of signing the ICF.
• Expected survival time of ≥3 months.
• Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC) with unresectable locally advanced stage (Stage ⅢB/ⅢC), metastatic or recurrent stage (Stage Ⅳ) that is not eligible for radical concurrent chemoradiotherapy, in accordance with the 8th edition of the TNM --Staging System for Lung Cancer by the International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC).
• Confirmed KRAS G12C mutation-positive by a qualified laboratory (CAP/CLIA or nationally accredited) using next-generation sequencing (NGS) or an equivalent method; positivity in either tissue samples or plasma circulating tumor DNA (ctDNA) is acceptable. If plasma testing is negative and tissue testing is feasible, supplementary tissue testing is recommended.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1.
• Definition for first-line systemic therapy of advanced disease: No prior systemic anti-tumor therapy for metastatic/advanced disease. For subjects who previously received radical post-surgical therapy, chemoradiotherapy or immunotherapy alone, enrollment is permitted only if the interval from the last dose to disease recurrence is ≥6 months.
• Presence of at least one measurable lesion in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; measurable lesions within a prior radiotherapy field or after local treatment may be selected as target lesions if disease progression is documented.
• Sufficient organ and bone marrow function, including the following:
• Adequate hematopoietic function: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥9 g/dL. No blood transfusion or treatment with granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), erythropoietin (EPO) or other similar agents is allowed within 14 days prior to blood routine testing.
• Adequate liver function: Total bilirubin (TBIL) \<1.5×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5×ULN; for subjects with Gilbert's syndrome, TBIL \<2×ULN is acceptable; for subjects with liver metastases from tumor, AST and ALT \<5.0×ULN is required; for subjects with extrahepatic obstruction confirmed by direct bilirubin (DBIL) testing, TBIL \<3.0×ULN is permitted.
• Adequate renal function: Serum creatinine (Cr) ≤1.5×ULN, or if Cr \>1.5×ULN, creatinine clearance (CrCl) ≥60 mL/min calculated by the Cockcroft-Gault formula.
• Adequate coagulation function: Prothrombin time (PT)/activated partial thromboplastin time (APTT) \<1.5×ULN, and international normalized ratio (INR) \<1.5 or within the target range for anticoagulant therapy.
• Serum magnesium level within the normal range.
• Toxic effects from prior anti-tumor therapy must have recovered to baseline levels (excluding residual alopecia) or grade ≤1 at enrollment (grade ≤2 neurotoxicity is acceptable). For immune-related adverse events (irAEs) involving the endocrine system caused by prior immunotherapy (e.g., immune-related hypothyroidism), subjects with well-controlled symptoms under stable-dose hormone replacement therapy or physiological-dose corticosteroid therapy may be enrolled if the investigator assesses that the treatment does not interfere with the administration of study drugs and safety evaluation.

You may not qualify if:

• Prior treatment with a KRAS G12C inhibitor or TROP2-ADC; any prior systemic anti-tumor therapy (chemotherapy, immunotherapy, targeted therapy, etc.) for advanced non-small cell lung cancer (NSCLC).
• Histologically or cytologically confirmed mixed NSCLC with small cell carcinoma components or predominantly squamous cell carcinoma components.
• Significant cardiovascular and cerebrovascular diseases, including:
• A confirmed major cardiovascular adverse event within 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or receipt of angioplasty, vascular stenting, coronary artery bypass grafting, or other similar procedures; -Clinically significant prolonged QT/QTcF interval on electrocardiogram (QTcF \>470 ms in females or QTcF \>450 ms in males); A confirmed major cerebrovascular adverse event within 3 months, such as intracerebral hemorrhage or cerebral infarction.
• Uncontrolled central nervous system (CNS) disease: active CNS metastases requiring urgent local therapy; meningeal carcinomatosis.
• Interstitial lung disease (ILD)/drug-induced pneumonitis: active ILD/pneumonitis or a history of ILD/pneumonitis requiring systemic corticosteroid therapy; baseline chest imaging showing active ILD-like changes.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Ruijin Hospital: collaborator
• The First Affiliated Hospital of University of Science and Technology of China: collaborator
• Affiliated Hospital of Jiaxing University: collaborator
• Huzhou Central Hospital: collaborator
• Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University: collaborator
• Ningbo Medical Center Lihuili Hospital: collaborator

Study Sites (1)

2nd Affiliated Hospital, School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

Central Study Contacts

Yang Xia, MD，PhD

CONTACT

+8618868439669; yxia@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: June 25, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 7, 2026

Record last verified: 2026-02

Locations

CN (1)