IBI351 Plus Cetuximab β in Untreated Advanced Non-small Cell Lung Cancer With KRAS G12C Mutation

NCT07198841 | Recruiting Phase 2

• 1 other identifier: CTONG2506
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 7

Brief Summary

Study Design: a Phase II, single-arm, multicenter, prospective, interventional study. Target Population: Subjects with previously untreated, locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed to harbor the KRAS G12C mutation. Treatment Regimen: All enrolled subjects will receive IBI351 combined with cetuximab β injection. Treatment will continue until disease progression (as assessed by the investigator per RECIST 1.1 criteria) or the occurrence of intolerable toxicity. Primary Endpoint: Objective Response Rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary Endpoints: Disease Control Rate (DCR), Time to Response (TTR), Progression-Free Survival (PFS), and Overall Survival (OS) , and safety.

Conditions

Lung Cancer (Non-Small Cell)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The proportion of patients achieving complete and partial response after treatment, measured according to RECIST v1.1 criteria

  From the first dose of treatment to disease progression or death, whichever comes first, up to 2 years

Secondary Outcomes (5)

• Progression-Free Survival

  From the first dose of treatment until the first documentation of disease progression or death from any cause, whichever occurs first (up to 2 years)

• Time To Response

  From the first dose to disease progression or death, whichever comes first, up to 2 years

• Disease Control Rate

  From the first dose to disease progression or death, whichever comes first, up to 2 years

• Overall Survival

  From the first dose of treatment to death due to any reason, whichever comes first, up to 2 years

• Adverse Events

  From the first dose of treatment to disease progression or death (up to 2 years)

Study Arms (1)

IBI351+ cetuximab β treatment

EXPERIMENTAL

Drug: IBI351 combined with cetuximab β

Interventions

IBI351 combined with cetuximab β DRUG

Subjects will receive treatment with IBI351 plus cetuximab β, consisting of oral IBI351 administered at 600 mg twice daily (BID) either in a fasting or fed state, combined with intravenous infusion of cetuximab β injection dosed at 500 mg/m² (body surface area) every two weeks. Each treatment cycle spans two weeks. Therapy will continue until disease progression, unacceptable toxicity, or meeting other protocol-defined criteria for treatment discontinuation-whichever occurs first. Dose adjustments may be implemented throughout the study based on drug-related toxicities.

IBI351+ cetuximab β treatment

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.
• Life expectancy ≥ 3 months.
• Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB/IIIC), metastatic, or recurrent (Stage IV) non-small cell lung cancer (NSCLC), per the International Association for the Study of Lung Cancer (IASLC) and American Joint Committee on Cancer (AJCC) 8th edition TNM staging, and not candidates for curative concurrent chemoradiotherapy.
• Documented KRAS G12C mutation confirmed by a written report from a certified laboratory.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
• No prior systemic anti-tumor therapy for locally advanced or metastatic non-squamous NSCLC. Subjects who received prior adjuvant therapy are eligible provided disease recurrence occurred ≥6 months after the last dose of adjuvant therapy or the last session of radical radiotherapy.
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Lesions within a prior radiation field or after local therapy can be considered target lesions if documented progression is evident.
• Adequate organ and bone marrow function, defined as:
• ）Hematopoietic: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 9 g/dL. No transfusion or treatment with granulocyte colony-stimulating factor (G-CSF), thrombopoietin, or erythropoietin within 14 days prior to hematology tests.
• ）Hepatic: 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, AST and ALT \< 5.0 × ULN is required. If direct bilirubin (DBIL) suggests extrahepatic obstruction, TBIL \< 3.0 × ULN is permitted.
• ）Renal: Serum creatinine (Cr) ≤ 1.5 × ULN OR calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula) if Cr \> 1.5 × ULN.
• ）Coagulation: Prothrombin time (PT) / activated partial thromboplastin time (APTT) \< 1.5 × ULN and international normalized ratio (INR) \< 1.5 or within the therapeutic range for subjects on anticoagulation therapy.
• ）Magnesium: Serum magnesium within normal limits. 10. Toxicities from prior anti-tumor therapy must have resolved to baseline or ≤ Grade 1 (except for residual alopecia; neurotoxicity ≤ Grade 2 is acceptable). Subjects with prior immune-related endocrine adverse events (irAEs) from immunotherapy (e.g., hypothyroidism) that are asymptomatic and stably controlled with ongoing hormone replacement or physiologic doses of corticosteroids may be enrolled if the investigator judges that this will not affect study drug administration or safety assessment.
• \. Female subjects of childbearing potential or male subjects with partners of childbearing potential must use effective contraception from signing the ICF until 6 months after the last dose of study drug. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days (inclusive) prior to the first dose. If a urine pregnancy test result is inconclusive, a serum pregnancy test is required.

You may not qualify if:

• Histologically or cytologically confirmed NSCLC with mixed small cell components or predominantly squamous cell carcinoma components.
• Presence of EGFR sensitizing mutation, ALK rearrangement, ROS-1 fusion, or other genomic alterations for which NMPA-approved first-line NSCLC therapies exist.
• Significant cardiovascular or cerebrovascular disease, including:
• ）Clinically significant cardiovascular events within 6 months (e.g., myocardial infarction, angina, heart failure, severe arrhythmia) or history of angioplasty, stenting, or coronary artery bypass grafting.
• ）Clinically significant prolongation of the QTcF interval (QTcF \> 470 ms for females or \> 450 ms for males).
• ）Clinically significant cerebrovascular events within 3 months (e.g., cerebral hemorrhage, infarction).
• \. Active central nervous system (CNS) metastases (e.g., brain or leptomeningeal metastases). Subjects with previously treated brain metastases may be eligible if they are asymptomatic for at least 7 days after completion of radiotherapy/local therapy without requiring steroids/anti-epileptics, OR off steroids/anti-epileptics for at least 7 days, AND judged by the investigator to have stable CNS disease.
• \. Clinically significant interstitial lung disease (ILD), radiation pneumonitis, or drug-induced pneumonitis requiring treatment; active pulmonary tuberculosis; pneumoconiosis; Grade ≥2 pneumonitis of other etiologies; or severely impaired pulmonary function (FEV1 or DLCO or DLCO/VA \<40% of predicted value).
• \. Significant gastrointestinal disorders affecting drug absorption or swallowing (e.g., refractory hiccups, nausea, vomiting, severe peptic ulcer disease, liver cirrhosis, active GI bleeding).
• \. Major active or chronic infections, including:
• Active infection requiring systemic therapy.
• Baseline positive HIV antibody (HIV-Ab); acute or chronic active hepatitis B (defined as HBsAg and/or HBcAb positive AND HBV-DNA \> 2500 copies/mL or 500 IU/mL); or acute or chronic active hepatitis C (HCV antibody positive AND HCV-RNA above the lower limit of quantification).
• Active pulmonary tuberculosis. 8. Symptomatic pleural, peritoneal, or pericardial effusions requiring repeated drainage.
• \. Poorly controlled systemic diseases despite standard therapy (e.g., hypertension: systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg; diabetes).
• \. History of other active malignancies within 2 years prior to study entry, except appropriately treated carcinoma in situ of the cervix, localized squamous cell carcinoma of the skin, basal cell carcinoma, prostate cancer not requiring treatment, ductal carcinoma in situ of the breast, and superficial non-muscle invasive urothelial carcinoma.

Sponsors & Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.: collaborator
• Guangdong Association of Clinical Trials: lead
• Mabpharm Limitied: collaborator

Study Sites (7)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University,

Guangzhou, Guangdong, 510080, China

RECRUITING

Chinese PLA General Hospital

Beijing, China

RECRUITING

The First People's Hospital of Foshan

Foshan, China

RECRUITING

The first affiliated hospital of nanchang university

Nanchang, China

RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, China

RECRUITING

Affiliated Tumor Hospital of Guangxi Medical University

Nanning, China

NOT YET RECRUITING

The Fourth Hospital of Hebei Medical University

Shijiazhuang, China

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Qing Zhou, PhD

CONTACT

+86 20 83827812; gzzhouqing@126.com

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: August 27, 2025
• First Posted: September 30, 2025
• Study Start: November 3, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 11, 2026

Record last verified: 2025-11

Locations

CN (7)