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

Recruiting now · Phase 3

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

In brief

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.

Key facts

Study ID

NCT04181060

Run by

National Cancer Institute (NCI)

People needed

300

Starts

2020-12-28

Expected to finish

2026-12-31

Last updated by the study team

2026-08-07

Who can join

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

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
• 6 weeks after the last dose of protocol treatment for female patients on the osimertinib (AZD9291) alone arm
• 4 months after the last dose of protocol treatment for male patients on osimertinib (AZD9291) alone arm
• 6 months after the last dose of protocol treatment for all patients on osimertinib (AZD9291) plus bevacizumab combination arm
• NOTE: Female patients should also not breastfeed while on treatment and for 6 months after the last dose bevacizumab
• Leukocytes >= 3,000/mcL (obtained =< 14 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 14 days prior to randomization)
• Platelets >= 100,000/mcL (obtained =< 14 days prior to randomization)
• Hemoglobin >= 9 g/dL (obtained =< 14 days prior to randomization)
• Total bilirubin and creatinine =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 14 days prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 14 days prior to randomization)

Where it is running

• Kaiser Permanente-South Sacramento — Sacramento, California, United States (enrolling)
• Kaiser San Rafael-Gallinas — San Rafael, California, United States (enrolling)
• Kaiser Permanente-Richmond — Richmond, California, United States (enrolling)
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (enrolling)
• Kaiser Permanente-Santa Teresa-San Jose — San Jose, California, United States (enrolling)
• Kaiser Permanente San Leandro — San Leandro, California, United States (enrolling)
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States (enrolling)
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States (enrolling)
• Cancer Center at Saint Joseph's — Phoenix, Arizona, United States (enrolling)
• Kaiser Permanente Downtown Commons — Sacramento, California, United States (enrolling)
• Kaiser Permanente-San Francisco — San Francisco, California, United States (enrolling)
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro — Jonesboro, Arkansas, United States (enrolling)
• Kaiser Permanente-Deer Valley Medical Center — Antioch, California, United States (enrolling)
• Katmai Oncology Group — Anchorage, Alaska, United States (enrolling)
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States (enrolling)
• Kaiser Permanente Dublin — Dublin, California, United States (enrolling)
• Kaiser Permanente-Fremont — Fremont, California, United States (enrolling)
• Washington Health — Fremont, California, United States (enrolling)
• Kaiser Permanente Fresno Orchard Plaza — Fresno, California, United States (enrolling)
• Kaiser Permanente-Fresno — Fresno, California, United States (enrolling)
• Kaiser Permanente-Roseville — Roseville, California, United States (enrolling)
• Kaiser Permanente- Modesto MOB II — Modesto, California, United States (enrolling)
• Kaiser Permanente-Modesto — Modesto, California, United States (enrolling)
• Kaiser Permanente-Oakland — Oakland, California, United States (enrolling)
• Kaiser Permanente Medical Center - Santa Clara — Santa Clara, California, United States (enrolling)

Full record on ClinicalTrials.gov

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