Osimertinib +/− Bevacizumab for Lung Cancer with Brain Metastasis

Not currently recruiting at 18 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers

Disqualifiers: Symptomatic brain metastases, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of osimertinib, with or without bevacizumab, in treating lung cancer that has spread to the brain. Osimertinib aims to stop cancer cell growth, while bevacizumab (also known as Avastin) may slow cancer by blocking new blood vessel growth. The trial targets individuals with non-small cell lung cancer featuring a specific EGFR mutation and brain metastases that are not causing symptoms. Participants must not have received certain cancer drugs previously. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you should avoid medications or supplements that strongly affect CYP3A4 (an enzyme that helps process drugs in the body). It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that combining the drugs osimertinib and bevacizumab produced promising results for patients with a specific type of lung cancer that had spread to the brain. Most patients managed the side effects without major issues. Another study found that osimertinib alone helped patients with brain metastases, though not everyone benefited equally.

When used together, osimertinib and bevacizumab significantly extended the time patients lived without their brain cancer worsening. This suggests the treatment might be effective and manageable for individuals with this type of lung cancer. However, the treatment remains under study, and individual experiences may vary. It is crucial to consult a healthcare provider about potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer with brain metastasis because they bring a unique approach to tackling the disease. Unlike many current treatments that focus solely on the primary lung tumors, osimertinib is a targeted therapy that specifically targets and inhibits the epidermal growth factor receptor (EGFR) mutations often found in these cancer cells, potentially offering a more precise treatment. Additionally, the combination of osimertinib with bevacizumab, an anti-angiogenic drug, aims to cut off the blood supply to tumors, which could enhance the treatment’s effectiveness. This dual approach could lead to improved outcomes for patients by attacking the cancer on multiple fronts.

What evidence suggests that this trial's treatments could be effective for lung cancer with brain metastasis?

Research shows that osimertinib, one of the treatments in this trial, effectively treats non-small cell lung cancer that has spread to the brain. In earlier studies, patients taking osimertinib kept their cancer under control for about 8.8 months on average. It also reduced the risk of cancer worsening in the brain by about 52% compared to other treatments.

In this trial, some participants will receive osimertinib with bevacizumab, while others will receive osimertinib alone. Previous studies have shown that combining osimertinib with bevacizumab helps patients live longer without their brain cancer worsening. While this combination offers additional benefits over osimertinib alone, it does not necessarily extend overall survival. ^{1 2 3 6 7}

Who Is on the Research Team?

Sarah B. Goldberg

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer that has an EGFR mutation and spread to the brain. They should have a life expectancy over 3 months, be willing to use contraception, and not be breastfeeding or pregnant. No prior EGFR TKI treatment or immunotherapy is allowed, and they mustn't have symptomatic brain metastases or other active cancers.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My lung cancer has a specific change in the EGFR gene.

My cancer can be measured by scans or physical exams, but it's not a must.

Exclusion Criteria

I have had lung conditions that needed steroid treatment.

You are allergic to Chinese hamster ovary cell products or other genetically engineered human antibodies.

Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive osimertinib with or without bevacizumab in 21-day cycles, with regular CT scans, MRIs, tumor biopsies, and blood sample collections

Up to 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Osimertinib

Trial Overview The study tests if osimertinib alone or combined with bevacizumab is more effective for patients whose lung cancer has spread to the brain. Osimertinib blocks enzymes needed by tumor cells; bevacizumab may prevent tumor growth by inhibiting blood vessel formation.

How Is the Trial Designed?

Group I: Arm II (osimertinib) Experimental Treatment 1 Intervention

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 CT scan, MRI, tumor biopsy and blood sample collection throughout the study.

Group II: Arm I (osimertinib, bevacizumab) Experimental Treatment 6 Interventions

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 CT scan, MRI, tumor biopsy and blood sample collection throughout the study.

Osimertinib is already approved in United States, European Union for the following indications:

Approved in United States as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Approved in European Union as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a study of 37 patients with EGFR-mutant non-small cell lung cancer and untreated brain metastases, osimertinib showed a 1-year cumulative incidence of local recurrence in the brain of only 14%, with significantly lower rates (less than 4%) in patients achieving a complete or partial response.

Factors such as uncontrolled primary tumors, a higher number of prior systemic therapies, and worse performance status (ECOG score) were associated with increased risk of local recurrence, indicating that these patients may require closer monitoring and potential additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer. Hui, C., Qu, V., Wang, JY., et al.[2022]

Osimertinib, an EGFR inhibitor, shows promise as an effective treatment for patients with untreated non-small cell lung cancer that has spread to the brain.

In clinical studies, osimertinib demonstrated longer median progression-free survival and higher objective response rates compared to older EGFR inhibitors like gefitinib and erlotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib Treats CNS Metastases in NSCLC. [2022]

In a study of 52 treatment-naïve NSCLC patients with brain metastasis and EGFR mutations, the combination of osimertinib and bevacizumab resulted in a high objective response rate of 75% and a median progression-free survival of 17 months.

The treatment was well-tolerated, with manageable side effects such as mild-to-moderate hand-foot syndrome and hypertension, indicating that this combination therapy could be a promising option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib combined with bevacizumab as the first-line treatment in non-small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations. Zhang, L., You, Y., Liu, X., et al.[2023]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6656518/

Osimertinib for EGFR‐Mutant Lung Cancer with Brain ... Of the 40 patients with brain metastases, the median TTF was 10.0 months (95% confidence interval [CI] 6.2–13.9), PFS was 8.8 months (95% CI, 6.3–11.3), and OS ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500224000734

Osimertinib plus local treatment for brain metastases ... Single-agent osimertinib has improved outcomes in EGFR-mutated lung cancer patients with brain metastases (BMs), but still, 40 % of them will experience an ...

3. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2023/tagrisso-osimertinib-plus-chemotherapy-reduced-the-risk-of-disease-progression-in-the-brain-by-42-percent-in-patients-with-egfr-mutated-advanced-lung-cancer-and-brain-metastases-at-baseline-10212023.html

TAGRISSO® (osimertinib) plus chemotherapy reduced the ... TAGRISSO with the addition of chemotherapy reduced the risk of CNS disease progression or death by 42% compared to TAGRISSO alone.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10730363/

Intracranial Outcomes of De Novo Brain Metastases Treated ... Two-year overall survival was 80%. CNS progression rates at 1-, 2-, and 3-years post-osimertinib were 21%, 32%, and 41%, respectively.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02219

CNS Efficacy of Osimertinib With or Without Chemotherapy ... Osimertinib was associated with a 52% reduction in the risk of CNS progression or death from any cause versus comparator EGFR-TKIs (erlotinib or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7097701/

Assessment of Effectiveness and Safety of Osimertinib for ... This systematic review and meta-analysis assesses the effectiveness and safety of osimertinib in the management of intracranial metastatic disease.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8556

Comparative efficacy of osimertinib with and without ... Conclusions: Combining Osimertinib with stereotactic radiation or radiosurgery improves survival in NSCLC with brain metastases but may increase ...