NCT04181060|RecruitingPhase 3FDA Drug

Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer

Randomized Phase III Study of Combination Osimertinib (AZD9291) and Bevacizumab Versus Osimertinib (AZD9291) Alone as First-Line Treatment for Patients With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2019-07941EA5182U10CA180820

Study Type

interventional

Target

300

Locations

1 country

Sites

604

Timeline

RegisteredNov 2019

StartedDec 2020

CompletionDec 2026

Brief Summary

This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

300

participants targeted

Target at P50-P75 for phase_3

Timeline

8mo left

Started Dec 2020

Longer than P75 for phase_3

Geographic Reach

1 country

604 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6 years study duration

Study Progress89%

Dec 2020Dec 2026

First Submitted

Initial submission to the registry

November 27, 2019

Completed

2 days until next milestone

First Posted

Study publicly available on registry

November 29, 2019

Completed

1.1 years until next milestone

Study Start

First participant enrolled

December 28, 2020

Completed

6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

May 6, 2026

Status Verified

November 1, 2025

Enrollment Period

6 years

First QC Date

November 27, 2019

Last Update Submit

May 5, 2026

Conditions

Stage IIIB Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Advanced Lung Non-Squamous Non-Small Cell Carcinoma Recurrent Lung Non-Squamous Non-Small Cell Carcinoma Metastatic Lung Non-Squamous Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

Progression-free survival (PFS)
Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. PFS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 2.5%.
From randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever occurs first, assessed up to 10 years

Secondary Outcomes (5)

Overall survival (OS)
From randomization to death from any cause, assessed up to 10 years
Best objective response rate
Up to 10 years
Time to central nervous system progression
From study randomization to evidence of central nervous system progressive disease, with death and progression as competing events, assessed up to 10 years
Central nervous system progression-free survival
From study randomization to evidence of central nervous system progressive disease or death from any cause, whichever occurs first, assessed up to 10 years
Incidence of adverse events
Up to 30 days after the last administration of investigational agent

Other Outcomes (2)

Mechanisms of resistance to AZD9291 (osimertinib) and AZD9291 (osimertinib) with bevacizumab first-line therapy through post-progression circulating tumor-derived deoxyribonucleic acid (ctDNA)
Up to 10 years
Circulating tumor deoxyribonucleic acid (ctDNA) clearance on study treatment
Up to 10 years

Study Arms (2)

Arm A (osimertinib)

ACTIVE COMPARATOR

Patients receive osimertinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, MUGA, CT and may undergo MRI and blood and urine sample collection on study.

Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Echocardiography TestProcedure: Magnetic Resonance ImagingProcedure: Multigated Acquisition ScanDrug: Osimertinib

Arm B (osimertinib, bevacizumab)

EXPERIMENTAL

Patients receive osimertinib PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, MUGA, CT and may undergo MRI and blood and urine sample collection on study.

Biological: BevacizumabProcedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Echocardiography TestProcedure: Magnetic Resonance ImagingProcedure: Multigated Acquisition ScanDrug: Osimertinib

Interventions

BevacizumabBIOLOGICAL

Given IV

Also known as: ABP 215, ABP-215, ABP215, Alymsys, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Avzivi, Aybintio, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MB02, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-aybi, Bevacizumab-bvzr, Bevacizumab-equi, Bevacizumab-maly, Bevacizumab-onbe, Bevacizumab-tnjn, BP102, BP102 Biosimilar, CT P16, CT-P16, CTP16, Equidacent, FKB 238, FKB-238, FKB238, 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, MB 02, MB-02, MB02, Mvasi, MYL-1402O, Onbevzi, Oyavas, PF 06439535, PF-06439535, PF06439535, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

Arm B (osimertinib, bevacizumab)

Biospecimen CollectionPROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (osimertinib)Arm B (osimertinib, bevacizumab)

Computed TomographyPROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (osimertinib)Arm B (osimertinib, bevacizumab)

Echocardiography TestPROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm A (osimertinib)Arm B (osimertinib, bevacizumab)

Multigated Acquisition ScanPROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Arm A (osimertinib)Arm B (osimertinib, bevacizumab)

OsimertinibDRUG

Given PO

Also known as: AZD 9291, AZD-9291, AZD9291, Mereletinib

Arm A (osimertinib)Arm B (osimertinib, bevacizumab)

Magnetic Resonance ImagingPROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (osimertinib)Arm B (osimertinib, bevacizumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patient must have a pathologically-confirmed diagnosis of non-squamous, non-small cell lung cancer (NSCLC)
Patient must have advanced disease, defined as - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria
Patient must have somatic activating sensitizing mutation in EGFR (e.g. but not limited to Exon 19 deletion, L858R, E709X, G719X, exon 19 insertions, L861Q, S768I). Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible. Test results originating from a Clinical Laboratory Improvement Act (CLIA)-certified or similarly accredited laboratory are acceptable; no specific assay is mandated. Plasma, cytology, or tumor tissue can be utilized for mutation testing
Patient must not have received any prior treatment with an anti-VEGF agent
NOTE: Prior treatment with an EGFR TKI is not allowed, however if a candidate for this study has already started osimertinib within 21 days prior to randomization, the exact osimertinib start date is known, and the patient had the required study baseline imaging completed prior to the osimertinib start date, the patient will be eligible
Patients that have received prior radiation therapy are eligible. Radiation (limited field stereotactic radiation or conventional radiation) must have been completed at least one week prior to study drug initiation and more extensive field radiation (i.e., whole-brain radiotherapy \[WBRT\]) must have been completed at least two weeks prior to drug initiation
Patient must not have any risk factors for anti-VEGF administration, specifically, hemoptysis, active cardiovascular disease, uncontrolled hypertension, significant proteinuria (screening urinalysis \> 300 mg/dl) and tumor invading major blood vessels
Patient must have measurable disease. Baseline measurements of sites of disease must be obtained within 4 weeks prior to study randomization. If a potential target lesion is previously irradiated without subsequent growth and/or is radiated after the imaging from which baseline measurements are obtained, they cannot be included as target lesions, and additional target lesions are required to meet criteria for measurable disease
Patient must not have had any prior systemic treatment for metastatic disease
Patient must be ≥ 18 years of age
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patient of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for 2 weeks prior to the start of treatment, while on study treatment, and for
+28 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (604)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

SUSPENDED

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

SUSPENDED

Alaska Breast Care and Surgery LLC