Brigatinib and Bevacizumab for the Treatment of ALK-Rearranged Locally Advanced, Metastatic, or Recurrent NSCLC

Running, not enrolling · Phase 1

Conditions studied: Locally Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8

In brief

This phase Ib trial studies the side effects and best dose of brigatinib and how well it works with bevacizumab in treating patients with ALK-rearranged non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic) or has come back (recurrent). Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known if brigatinib and bevacizumab will work better in treating patients with ALK-rearranged non-small cell lung cancer.

Key facts

Study ID

NCT04227028

Run by

City of Hope Medical Center

People needed

5

Starts

2020-03-09

Expected to finish

2027-03-25

Last updated by the study team

2026-07-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have a histologically documented (either primary or metastatic site) diagnosis of locally advanced, recurrent, or metastatic ALK rearranged non-small cell lung cancer (NSCLC)
• Patients must have shown progression on ALK-directed therapy
• Note: Patients may have received more than one prior line of therapy, however, at least one of these must be an ALK-directed line of therapy
• Patients must have measurable disease as per appropriate guidelines by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• Patients must have the ability to understand and the willingness to sign a written consent prior to registration in the study
• Patients with asymptomatic (as determined by the treating investigator) CNS metastasis are eligible for participation
• Note: Patients with leptomeningeal disease are not eligible
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Patient life expectancy of more than 12 weeks
• Patients must have adequate organ and bone marrow function during screening, as defined below:
• Absolute neutrophil count >= 1.5 x 10\^9/L
• Hemoglobin >= 9 g/dL
• Note: Transfusions are permitted (transfusions >= 1 day to registration are allowed)
• Platelets >= 75 x 10\^(9)/L
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Note: Patients with Gilbert syndrome are exempt
• Alanine amino transferase and aspartate aminotransferase =< 2.5 x ULN
• Note: =< 5 x ULN is acceptable if liver metastases are present
• Serum lipase =< 1.5 x ULN
• Creatine kinase (CPK) < 5.0 x ULN
• Estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) equation >= 30 mL/min/1.73 m\^2
• Patients must meet criteria for appropriate contraception, listed as follows
• Female patients must meet at least one of the following criteria:
• Are postmenopausal with last menstrual period at least 1 year before registration, OR
• Are surgically sterile, OR

You may not qualify if…

• Patients who have had prior systemic anticancer or radiotherapy =< 14 days prior to first dose of brigatinib are not eligible
• Patients may not have received any other investigational agents =< 14 days prior to first dose of brigatinib
• Patients who have received antineoplastic monoclonal antibodies within 21 days of the first dose of brigatinib, and tyrosine kinase inhibitors (TKIs) within 7 days of the first dose of brigatinib are not eligible
• Patients with prior severe infusion reaction to bevacizumab are not eligible
• Patients with other coexisting malignancies or malignancies diagnosed within the previous 3 years that per the investigator are at high-risk of relapse within one year are not eligible
• Note: Exceptions to this include non-melanoma skin cancer, cervical cancer in-situ, well-differentiated thyroid cancer or prostate cancer. Other cancers that per assessment of the principal investigator (PI) are not prognosis-limiting can be allowed after review by the PI. If there is no evidence of disease for at least 3 years, patients may be eligible
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Uncontrolled pulmonary, renal, or hepatic dysfunction,
• Ongoing or active infection requiring systemic treatment including hepatitis B and hepatitis C,
• Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection,
• Note: Patients who have isolated positive hepatitis B core antibody (i.e. in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load
• Active uncontrolled infection or severe infectious disease such as severe pneumonia, meningitis, or septicemia,
• Known active or chronic viral hepatitis or human immunodeficiency virus (HIV),
• Psychiatric illness/social situations that would limit compliance with study requirements
• Patients with any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints are not eligible
• Female patients who are pregnant, planning a pregnancy, or nursing or have a positive serum pregnancy test within 7 days prior registration (without subsequent negative vaginal ultrasound) are not eligible
• Patients who have had major surgery within 30 days of registration, are not eligible
• Note: Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed
• Patients who have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to the following are not eligible:
• Myocardial infarction within 6 months before registration
• Unstable angina within 6 months before registration
• Congestive heart failure within 6 months before registration
• History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician
• Any history of clinically significant ventricular arrhythmia
• Patients who have had a cerebrovascular accident or transient ischemic attack within 6 months before registration are not eligible

Where it is running

• City of Hope Medical Center — Duarte, California, United States
• University of Colorado Cancer Center — Aurora, Colorado, United States
• Northwestern University — Chicago, Illinois, United States
• Rush University Medical Center — Chicago, Illinois, United States
• Penn State Cancer Institute — Hershey, Pennsylvania, United States
• University of Wisconsin Hospital and Clinics — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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