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

NCT04227028 | Active Not Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: 20495STU00211030NU 19L01P30CA060553NCI-2019-08726
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) 5.0.

  Within 30 days of treatment discontinuation or prior to start of next treatment

• Maximum tolerated dose

  Will be determined by dose limiting toxicities and assessed using CTCAE 5.0.

  Up to 28 days

Secondary Outcomes (5)

• Dose-limiting toxicities

  Up to 28 days

• Overall response rate

  Up to 3 years

• Duration of response

  From first documentation of clinical benefit from treatment to the time of documentation of progressive disease or death, whichever comes first, assessed up to 3 years

• Progression-free survival (PFS)

  From treatment initiation to the time of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years

• Overall survival (OS)

  From treatment initiation until death due to any cause, assessed up to 3 years

Study Arms (1)

Treatment (brigatinib, bevacizumab)

EXPERIMENTAL

Patients receive brigatinib PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive bevacizumab IV on day 8 of cycle 1 and day 1 of subsequent cycles. Starting cycle 2, cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Drug: Brigatinib

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501

Treatment (brigatinib, bevacizumab)

Brigatinib DRUG

Given PO

Also known as: Alunbrig, AP 26113, AP-26113, AP26113

Treatment (brigatinib, bevacizumab)

Eligibility Criteria

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

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)

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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; brigatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial 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; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Victoria M. Villaflor, M.D.

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 13, 2020
• Study Start: March 9, 2020
• Primary Completion: April 21, 2026
• Study Completion: April 21, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

US (6)