Osimertinib + Ramucirumab for Lung Cancer

Not currently recruiting at 12 trial locations

Overseen By Chul Kim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Xiuning Le

Must not be taking: CYP3A4 inducers, QT prolongers

Disqualifiers: Other cancer, EGFR TKIs, 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: Unknown

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, osimertinib (a targeted therapy) and ramucirumab (a monoclonal antibody), to determine if they are more effective at preventing the progression of lung cancer compared to osimertinib alone. The trial targets individuals with non-small cell lung cancer that has specific genetic mutations and has either metastasized or cannot be treated with surgery or radiation. It seeks participants with these specific lung cancer mutations who can take pills. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop using medications that are strong inducers of CYP3A4 or known to prolong the QT interval. If you are taking such medications, you will need to stop them to participate in the trial.

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

Research has shown that the combination of osimertinib and ramucirumab has been tested before. In one study, 76% of patients responded well to this treatment. The study also found that most people tolerated the treatment well, although specific details about side effects were not provided.

Studies have shown that osimertinib alone is generally safe. Most side effects were mild or moderate, with only a small number (0.7%) of severe cases reported.

In summary, both the combination treatment and osimertinib alone have been used in people with lung cancer and are generally considered safe. However, like any treatment, side effects may occur, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Osimertinib with Ramucirumab for lung cancer because it offers a unique approach to treatment. Most current treatments focus on inhibiting cancer cell growth through well-known pathways, but this combination targets both the epidermal growth factor receptor (EGFR) with Osimertinib and the vascular endothelial growth factor receptor 2 (VEGFR2) with Ramucirumab. This dual action could potentially halt cancer progression more effectively by not only disrupting the cancer cells' growth signals but also cutting off their blood supply. This innovative combo might enhance treatment effectiveness and offer renewed hope for patients who haven't responded well to standard therapies.

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

This trial will compare the effectiveness of two treatment approaches for lung cancer. In one arm, participants will receive osimertinib alone. Studies have shown that this treatment helps many patients with EGFR-mutant non-small cell lung cancer live without cancer progression for about 20 months. In the other arm, participants will receive a combination of osimertinib and ramucirumab. Research has shown that this combination can extend the time patients live without disease worsening, offering hope for improved outcomes. By employing two different methods to halt tumor growth, this combination attacks cancer more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Xiuning Le, MD PhD

Principal Investigator

MD Anderson

Are You a Good Fit for This Trial?

Adults with non-squamous, non-small cell lung cancer (NSCLC) that has specific EGFR mutations and is advanced or metastatic. Participants must be able to swallow pills, have good organ function, no significant bleeding risks or recent serious blood clots, and not have had certain other cancers in the last 2 years. They should not have used drugs like osimertinib before and need to use contraception if of childbearing potential.

Inclusion Criteria

Your platelet count should be at least 100,000 per cubic millimeter.

My brain metastases are stable, treated, or symptom-free, and I'm on low or no steroids.

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

Exclusion Criteria

I have had a GI perforation or am at risk for one in the last 6 months.

My high blood pressure has not been controlled with medication for over 4 weeks.

I have had severe GI bleeding in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either osimertinib plus ramucirumab or osimertinib alone

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Osimertinib
• Ramucirumab

Trial Overview

The trial tests whether adding Ramucirumab to Osimertinib improves progression-free survival compared to using Osimertinib alone in NSCLC patients. Progression-free survival means how long patients live without their disease getting worse. The study randomly assigns participants into two groups following a 2:1 ratio favoring the combination treatment.

How Is the Trial Designed?

Group I: Arm B (Osimertinib) Active Control 1 Intervention

Osimertinib

Group II: Arm A (Osimertinib and Ramucirumab) Active Control 2 Interventions

Osimertinib and Ramucirumab

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?

Xiuning Le

Lead Sponsor

Trials

1

Recruited

160+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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 (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]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

In a study of 94 patients with advanced non-small-cell lung cancer (NSCLC) who had previously been treated, osimertinib showed a 47.3% overall objective response rate and a 90.1% disease control rate, indicating its effectiveness in this population.

Patients with the T790M mutation experienced significantly longer progression-free survival (PFS) compared to those without the mutation, highlighting osimertinib's targeted efficacy, especially in those with specific genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. Mu, Y., Xing, P., Hao, X., et al.[2022]

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

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]

In a study involving six patients with EGFR-mutated lung adenocarcinoma, the combination of osimertinib and ramucirumab was found to be generally safe, with only one case of dose-limiting toxicity (grade 3 appetite loss) and no other severe adverse events reported.

Five out of six patients showed a partial response to the treatment, with a median progression-free survival of 9.2 months for those with the EGFR T790M mutation, suggesting promising efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. Akamatsu, H., Ozawa, Y., Oyanagi, J., et al.[2023]

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]

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]

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