Bevacizumab Combined With Double Doses of Icotinib in Advanced NSCLC Patients With EGFR L858R Mutation

NCT05263947 | Completed Phase 2

• 1 other identifier: Beddi21
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, single-center, phase II trial designed to evaluate the efficacy and safety of bevacizumab combined with a double dose of icotinib as a first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC) harboring an EGFR Exon 21 L858R mutation. Patients will receive bevacizumab and icotinib (250 mg, administered orally three times per day ) until disease progression or unacceptable toxicity. The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity profile. The hypothesis is that the combination therapy will provide improved outcomes for this patient population, which typically has a poorer response to standard EGFR-TKI therapy.

Conditions

Carcinoma, Non-Small-Cell Lung; Bevacizumab; Tyrosine Kinase Inhibitor; EGFR L858R

Keywords

bevacizumab; icotinib; EGFR L858R; advanced non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS was defined as the time from the initial treatment to the first occurrence of disease progression or all-cause death (whichever occurs first ) assessed by the investigator according to RECIST v1.1.

  18 months

Secondary Outcomes (3)

• Overall survival(OS)

  44 months

• Objective response rate(ORR)

  up to 6 months

• Disease Control Rate (DCR)

  up to 6 months

Study Arms (1)

Bevacizumab Combined with Icotinib

EXPERIMENTAL

Participants receive bevacizumab 15 mg/kg by intravenous infusion once every 3 weeks, and oral icotinib 250 mg three times per day until disease progression or unacceptable toxicity.

Drug: Bevacizumab; Drug: Icotinib

Interventions

Bevacizumab DRUG

15 mg/kg, intravenous infusion, every three weeks

Bevacizumab Combined with Icotinib

Icotinib DRUG

Oral 250 mg, three times per day

Bevacizumab Combined with Icotinib

Eligibility Criteria

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

You may qualify if:

• Patients must meet ALL of the following criteria to be eligible for study enrollment:
• Voluntary provision of written informed consent prior to any study-specific procedures.
• Age ≥ 18 and ≤75 years at the time of signing informed consent.
• Willing and able to comply with the study protocol, as judged by the investigator.
• Histologically or cytologically confirmed, unresectable, locally advanced (Stage IIIB, not amenable to radical chemoradiotherapy), metastatic (Stage IV), or recurrent non-squamous non-small cell lung cancer (NSCLC) per the American Joint Committee on Cancer staging manual, eighth edition
• Documented EGFR exon 21 L858R mutation, as centrally confirmed by a high-sensitivity PCR-based test on tumor tissue. Results from direct sequencing are also acceptable.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of ≥ 12 weeks.
• Prior Therapy:
• No prior systemic cytotoxic chemotherapy for advanced or metastatic disease.
• Prior intra-cavitary cytotoxic agent administration for pleurodesis is excluded.
• Prior neoadjuvant or adjuvant chemotherapy is permitted if completed ≥ 6 months prior to enrollment.
• Prior radiotherapy is allowed provided:
• No thoracic radiotherapy within 28 days prior to enrollment.
• For radiotherapy outside the thorax, a washout period of ≥ 28 days from the last dose to enrollment is required. (For palliative radiotherapy to bone metastases within 2 weeks prior to enrollment, patients must have recovered from all related toxicities.)

You may not qualify if:

• Patients who meet ANY of the following criteria will be excluded from the study:
• History of mixed adenosquamous histology with predominant squamous component.
• Presence of any other concomitant EGFR mutation (e.g., exon 19 deletion, T790M) as detected by high-sensitivity testing (e.g., digital PCR).
• History or evidence of symptomatic or untreated central nervous system (CNS) metastases. Patients with previously treated CNS metastases are eligible if they are clinically stable and radiologically stable (without evidence of progression) for ≥ 28 days after CNS-directed therapy prior to enrollment.
• History of significant hemoptysis (\> 2.5 mL of bright red blood per episode) within 3 months prior to enrollment.
• Radiological evidence of tumor invasion or encasement of major blood vessels (e.g., pulmonary artery, superior vena cava).
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or anticipation of the need for major surgery during the study.
• Core biopsy or other minor surgical procedure (excluding placement of a vascular access device) within 7 days prior to the first dose of study treatment. Placement of a vascular access device must be completed at least 2 days prior to treatment initiation.
• Current or recent (within 10 days prior to initiation of bevacizumab) use of full-dose aspirin (\> 325 mg/day) or other NSAIDs known to inhibit platelet function.
• Current or recent (within 10 days prior to initiation of bevacizumab) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes. Prophylactic use of low-dose anticoagulants is permitted.
• Known hereditary or acquired bleeding diathesis or coagulopathy with a high risk of bleeding.
• Poorly controlled hypertension (systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg).
• History of hypertensive crisis or hypertensive encephalopathy.
• Significant cardiovascular disease within 6 months prior to enrollment, including but not limited to: cerebrovascular accident/transient ischemic attack, myocardial infarction, unstable angina, New York Heart Association (NYHA) Class II or greater congestive heart failure, or severe cardiac arrhythmia requiring medication that may interfere with the regularity of study treatment.
• Severe peripheral vascular disease (e.g., aortic aneurysm requiring surgical intervention, recent arterial thrombosis) within 6 months prior to enrollment.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; icotinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zhanyu Pan

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

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: January 18, 2022
• First Posted: March 3, 2022
• Study Start: January 30, 2022
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: February 24, 2026

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)