A Clinical Study on the Efficacy and Safety of the Combination of Limertinib and Bevacizumab Versus Limertinib as First-line Treatment for NSCLC.

NCT06982924 | Not Yet Recruiting Phase 2

• 1 other identifier: MR-31-25-032614
• Study Type: interventional
• Target: 136
• Locations: 0 countries
• Sites: N/A

Brief Summary

A prospective, controlled Phase II clinical study on the efficacy and safety of the combination of limertinib and bevacizumab versus limertinib monotherapy as first - line treatment for locally advanced or recurrent metastatic non - squamous NSCLC with EGFR mutations and high PD-L1 expression.

Conditions

EGFR Mutation Positive Advanced Non Small Cell Lung Cancer; PD-L1 Positive

Outcome Measures

Primary Outcomes (1)

• PFS

  the investigator assessed PFS

  About 2 years

Secondary Outcomes (2)

• ORR

  about 6 month

• OS

  About 2 years

Study Arms (2)

Experimental group

EXPERIMENTAL

Drug: Limertinib+bevacizumab

Control Group

PLACEBO COMPARATOR

Drug: Limertinib

Interventions

Limertinib+bevacizumab DRUG

The advanced or metastatic non-small cell lung cancer patients with EGFR mutation and high PD-L1 expression will receive the combination of Limertinib with bevacizuma in first-line treatment

Also known as: ASK120067

Experimental group

Limertinib DRUG

The advanced or metastatic non-small cell lung cancer patients with EGFR mutation and high PD-L1 expression will receive Limertinib in first-line treatment

Control Group

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent prior to any study - related procedures.
• Age ≥ 18 years.
• Histologically or cytologically confirmed non - squamous non - small cell lung cancer (NSCLC).
• Patients with locally advanced (IIIB - IIIC), metastatic, or recurrent (Stage IV) disease, as staged according to the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer (AJCC) 9th edition TNM staging for lung cancer, who are not candidates for surgical or radiation therapy.
• Confirmed EGFR - sensitive mutations (Ex19del, L858R) in tumor histology or cytology or in hematology.
• PD - L1 expression with a Combined Positive Score (CPS) ≥ 25%.
• ECOG performance status score of 0 - 1.
• No prior treatment with anti - angiogenic inhibitors or EGFR - TKIs.
• At least one radiologically measurable lesion, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions within a previously irradiated field may be considered measurable if progression has been confirmed.
• Asymptomatic or symptomatic - stable brain metastases after local treatment are allowed, provided that the following conditions are met: - Measurable disease outside the central nervous system (CNS). - No CNS symptoms or worsening of symptoms within the past 2 weeks. - No need for glucocorticoid treatment, or glucocorticoid treatment discontinued within 7 days prior to the first dose, or stable and reduced glucocorticoid dose to ≤ 10 mg/day prednisone (or equivalent) within 7 days prior to the first dose.
• Expected survival time \> 3 months.
• Adequate organ function, with the following laboratory values met by subjects: - Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L without the use of granulocyte - colony stimulating factor (G - CSF) within the past 14 days. - Platelets ≥ 100×10⁹/L without blood transfusion within the past 14 days. - Hemoglobin \> 9 g/dL without blood transfusion or use of erythropoiesis - stimulating agents within the past 14 days. - Total bilirubin ≤ 1.5× the upper limit of normal (ULN). - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN (for subjects with liver metastases, ALT or AST ≤ 5×ULN is allowed). - Serum creatinine ≤ 1.5×ULN and creatinine clearance (calculated using the Cockcroft - Gault formula) ≥ 60 ml/min. - Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5×ULN. - Normal thyroid function, defined as thyroid - stimulating hormone (TSH) within the normal range. Subjects may also be included if their baseline TSH is outside the normal range but their total T3 (or free T3) and free T4 are within the normal range. - Cardiac enzyme profile within the normal range (isolated laboratory abnormalities deemed not clinically significant by the investigator are also allowed).
• For women of childbearing age, a negative urine or serum pregnancy test must be conducted within 3 days prior to the first dose of the study drug (Day 1 of Cycle 1). If the urine pregnancy test result is inconclusive, a blood pregnancy test is required. Non - childbearing - age women are defined as those who have been post - menopausal for at least 1 year, or have undergone surgical sterilization or hysterectomy.
• All subjects (regardless of gender) with the potential for conception must use contraceptive measures with a failure rate of less than 1% throughout the entire treatment period and until 120 days (or 180 days) after the last dose of the study drug.

You may not qualify if:

• Pathologically diagnosed with small cell lung cancer (SCLC), including lung cancer with a mixture of SCLC and NSCLC.
• Patients who have received any EGFR - TKI treatment or anti - angiogenic therapy.
• Received the following treatments: - Systemic anti - tumor treatment such as chemotherapy, targeted therapy, or immunotherapy (including traditional Chinese medicine for anti - tumor purposes) within 3 weeks prior to treatment. - Any investigational drug treatment within 4 weeks prior to treatment. - High - dose immunosuppressive drugs (systemic glucocorticoids exceeding 10 mg/day prednisone or equivalent doses) within 4 weeks prior to treatment. - Attenuated live vaccines within 4 weeks prior to treatment (or planned to receive attenuated live vaccines during the study period). - Major surgery (such as open - cavity, open - chest, or laparotomy) within 4 weeks prior to treatment, or unresolved surgical wounds, ulcers, or fractures.
• Subjects who received chest radiotherapy with a dose greater than 30Gy within 6 months prior to treatment, or palliative radiotherapy with a dose of 30Gy or less within 7 days prior to treatment (palliative radiotherapy for bone lesions or intracranial lesions is allowed).
• Active autoimmune diseases that required systemic treatment (such as disease - modifying drugs, glucocorticoids, or immunosuppressants) within 2 years prior to the first dose of study drug. Replacement therapies (such as thyroid hormone, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic treatment.
• Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Known allergy to the active ingredients or excipients of the study drugs bevacizumab and lerotinib.
• Not fully recovered from the toxicity and/or complications caused by any intervention prior to the start of treatment (i.e., ≤ grade 1 or returned to baseline, excluding fatigue or hair loss).
• Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibodies).
• Subjects with active HCV infection (positive for HCV antibodies and HCV - RNA levels above the lower limit of detection).
• Received live vaccines within 30 days prior to the first dose of study drug (Day 1 of Cycle 1). Note: It is allowed to receive injectable inactivated virus vaccines for seasonal influenza within 30 days prior to the first dose of study drug 2: however, intranasal attenuated live influenza vaccines are not allowed. 14. Pregnant or lactating women.
• \. Any severe or uncontrolled systemic disease, such as: - Significant and symptomatic abnormalities in rhythm, conduction, or morphology on resting electrocardiogram that are difficult to control, such as complete left bundle branch block, second - degree or higher cardiac conduction block, ventricular arrhythmias, or atrial fibrillation. - Unstable angina, congestive heart failure, chronic heart failure with a New York Heart Association (NYHA) classification of ≥ Grade 2. - Myocardial infarction within 6 months prior to enrollment. - Poorly controlled blood pressure (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg). - History of non - infectious pneumonia that required glucocorticoid treatment within 1 year prior to the first dose of study drug, or current clinically active interstitial lung disease. - Active pulmonary tuberculosis. - Active or uncontrolled infections that require systemic treatment. - Clinically active diverticulitis, intra - abdominal abscess, or gastrointestinal obstruction. - Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis. - Poorly controlled diabetes (fasting blood glucose (FBG) \> 10 mmol/L). - Urine routine test indicating proteinuria ≥ ++, and confirmed 24 - hour urine protein quantification \> 1.0 g. - Subjects with mental disorders who are unable to cooperate with treatment.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Central Study Contacts

Zhong Runbo, MD

CONTACT

+86 021-62821990; zhongrb@shchest.org

Study Design

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

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 21, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: May 21, 2025

Record last verified: 2025-05