A Multicenter, Single-arm Phase II Study to Evaluate the Efficacy and Safety of Fulzerasib (IBI351) in Combination With Ivonescimab (AK-112) in First-line Treatment of Advanced or Metastatic Non-small Cell Lung Cancer Patients With KRAS G12C Mutation

NCT06936644 | Not Yet Recruiting Phase 2

• 1 other identifier: CIBI351IIS006
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

Brief Summary

A multicenter, single-arm Phase II study to evaluate the efficacy and safety of fulzerasib (IBI351) in combination with ivonescimab (AK-112) in first-line treatment of advanced or metastatic non-small cell lung cancer patients with KRAS G12C mutation

Conditions

KRAS G12C Lung Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  the investigator assessed objective response rate

  about 6 month

Study Arms (1)

The combination of IBI351 plus AK112

EXPERIMENTAL

Drug: IBI351+AK112

Interventions

IBI351+AK112 DRUG

The advanced or metastatic non-small cell lung cancer patients with KRAS G12C mutation will receive the combination of fulzerasib (IBI351) with ivonescimab (AK-112) in first-line treatment

Also known as: fulzerasib, ivonescimab

The combination of IBI351 plus AK112

Eligibility Criteria

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

You may qualify if:

• Sign the Informed Consent Form (ICF) and be able to comply with the visit and related procedures as stipulated in the protocol.
• Be male or female, aged ≥18 and ≤75 years old.
• Have an expected survival time of ≥6 months.
• Have histologically or cytologically confirmed locally advanced (IIIB/IIIC stage), metastatic or recurrent (IV stage) non-small cell lung cancer (NSCLC) that is not operable and not suitable for radical concurrent chemoradiotherapy, as classified by the 8th edition of the TNM staging system of the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer.
• All subjects must have a written test report before enrollment to prove the presence of KRAS G12C mutation; and must have no sensitive mutations of Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK), or other gene mutation types approved by the National Medical Products Administration (NMPA) for first-line treatment of NSCLC.
• Have at least one measurable lesion according to RECIST 1.1 criteria.
• Have not received any systemic anti-tumor treatment for locally advanced or metastatic NSCLC before; previous adjuvant therapy is allowed, but the interval between the last adjuvant therapy or last radical radiotherapy and disease recurrence should be at least 6 months.
• Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Have adequate organ and bone marrow function (subjects who have received any cell or growth factor therapy within 2 weeks before the first administration of the study drug should be excluded), defined as follows:
• \) Blood routine: Absolute neutrophil count (ANC) ≥1.5×109/L or within the normal range; platelet (PLT) count ≥100×109/L; hemoglobin (HGB) content ≥9.0 g/dL.
• \) Liver function: Serum total bilirubin (TBIL) ≤1.5×Upper Limit of Normal Value (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN.
• \) Renal function: Serum creatinine (Cr) ≤1.5×ULN or clearance of creatinine (CCr) ≥50 mL/min, calculated by the Cockcroft-Gault formula (using actual body weight); urine routine test shows urine protein \<2+; for subjects with urine protein ≥2+ at baseline as detected by urine test strips, a 24-hour urine collection should be performed and the protein content in 24-hour urine should be \<1 g (if both methods are used, the value obtained from 24-hour urine collection will be used to determine eligibility). 4) Coagulation function: Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN and International Normalized Ratio (INR) ≤ 1.5; 10. Female subjects of childbearing age or male subjects whose partners are of childbearing age must take effective contraceptive measures throughout the treatment period and for 180 days after the treatment.
• \. Female subjects have evidence of postmenopausal status, or the urine or serum pregnancy test results of premenopausal female subjects are negative.

You may not qualify if:

• Subjects should not be enrolled in this study if they meet any of the following criteria:
• \. Histological or cytological pathology confirms the presence of small cell carcinoma, neuroendocrine carcinoma, sarcoma, lymphoepithelioma-like carcinoma, salivary gland tumors, or mesenchymal tumor components.
• \. Have significant cardiovascular or cerebrovascular diseases, such as:
• Experienced definite cardiovascular abnormal events within 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or undergone angioplasty, vascular stent implantation, coronary artery bypass surgery, etc.
• Have clinically significant QT/QTcF interval prolongation (QTcF \> 470ms for females or \> 450ms for males).
• Experienced definite cerebrovascular abnormal events within 3 months, such as cerebral hemorrhage or cerebral infarction.
• \. Active central nervous system metastases (such as brain metastases or leptomeningeal metastases) are not eligible for enrollment. For subjects with brain metastases who have received radiotherapy or local treatment, if no hormones or antiepileptic drugs are used, they must be asymptomatic within at least 7 days after radiotherapy to be eligible for enrollment; if hormones or antiepileptic drugs are used, they must be asymptomatic within at least 7 days after drug withdrawal and the investigator deems the brain metastases to be stable, they can be eligible for enrollment; if stable brain metastases patients have not received radiotherapy or hormone or antiepileptic drug treatment, they can be eligible for enrollment after the investigator deems the brain metastases to be stable.
• \. Currently have clinically significant interstitial lung disease, radiation pneumonitis, drug-related pneumonitis, active pulmonary tuberculosis, pneumoconiosis, or have ≥ grade 2 other types of pneumonia, or have severe lung function impairment confirmed by pulmonary function tests (FEV1 or DLCO or DLCO/VA \< 40% of predicted values).
• \. Have significant gastrointestinal diseases, such as intractable hiccups, nausea, vomiting, severe gastrointestinal ulcers, liver cirrhosis, active gastrointestinal bleeding, or other diseases that affect swallowing tablets or significantly affect the absorption of oral drugs.
• \. Have major acute or chronic infections, including:
• Active infections requiring systemic treatment;
• Positive human immunodeficiency virus antibody (HIV-Ab) at baseline, acute or chronic active hepatitis B (defined as positive HBsAg and/or HBcAb and HBV-DNA copy number higher than 2500 copies/ml or 500IU/ml), or acute or chronic active hepatitis C (positive HCV antibody and HCV-RNA higher than the detection limit of the analytical method);
• Active pulmonary tuberculosis. 7. Accompanied by recurrent drainage or refractory pleural or peritoneal effusion or pericardial effusion.
• \. Accompanied by other poorly controlled systemic diseases, such as uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) or diabetes despite standard treatment.
• \. Have a history of significant bleeding tendency or coagulation disorders; have significant clinical bleeding symptoms within 4 weeks before enrollment, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing or expectorating ≥ 1 teaspoon of fresh blood or small blood clots or only coughing blood without sputum, subjects with blood in sputum are allowed to enroll), nasal bleeding (excluding epistaxis and retracted nasal blood); imaging studies during the screening period show that the tumor surrounds important blood vessels or has obvious necrosis or cavities, and the investigator deems that enrollment in the study would cause a bleeding risk.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead
• Innovent Biologics, Inc.: collaborator
• Akesobio: collaborator

Central Study Contacts

Zhong Runbo, MD

CONTACT

+86 021-62821990; zhongrb@shchest.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The chief physician of pneumology department

Model Details: the combination of IBI351 plus AK112

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: April 20, 2025
• Study Start: April 30, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: April 20, 2025

Record last verified: 2025-04