What side effects are associated with this type of intervention?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC), particularly EGFR Tyrosine Kinase Inhibitors (TKIs) like Osimertinib, often cause side effects such as diarrhea, rash, dry skin, and nail toxicity. Other EGFR TKIs, such as erlotinib and gefitinib, have similar side effects. Chemotherapy, which is frequently used in combination with TKIs, can lead to nausea, vomiting, fatigue, hair loss, and an increased risk of infection due to lowered blood cell counts. When these treatments are combined, the severity of these side effects can increase.

What prior FDA approvals exist?

Osimertinib is an FDA-approved EGFR tyrosine kinase inhibitor (TKI) used for the treatment of NSCLC with specific EGFR mutations. Other FDA-approved EGFR TKIs for NSCLC include erlotinib and gefitinib, which have shown efficacy in improving progression-free survival in patients with activating EGFR mutations. Additionally, afatinib and dacomitinib are approved for first-line treatment of metastatic NSCLC with non-resistant EGFR mutations. These drugs target the EGFR pathway, similar to osimertinib, and are part of the personalized treatment approach for NSCLC.

What other types of research exist?

Promising alternatives to Osimertinib for NSCLC patients include: 1) Combination of Pembrolizumab with platinum-doublet chemotherapy (e.g., carboplatin and pemetrexed), which has shown improved overall survival in the KEYNOTE-189 trial. 2) Lapatinib plus capecitabine, particularly for patients with brain metastases, as demonstrated in the LANDSCAPE trial. 3) Atezolizumab combined with carboplatin and etoposide, which is another effective regimen for extensive-stage small cell lung cancer and may be considered for certain NSCLC cases.

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Osimertinib + Chemotherapy for Lung Cancer (NeoADAURA Trial)

Phase 3

Waitlist Available

Led By Jamie Chaft, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC Staging Manual in Thoracic Oncology 2016])

Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a MDT evaluation (which should include a thoracic surgeon, specialised in oncologic procedures)

Must not have

Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

Mixed small cell and NSCLC histology

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of randomization to an average of 12 weeks after the first dose

Awards & highlights

Pivotal Trial

Summary

This trial is testing osimertinib, a drug that targets cancer cells, either by itself or with chemotherapy. It focuses on patients with a specific type of lung cancer that has a mutation in the EGFR gene. The drug works by stopping the growth of cancer cells.

Who is the study for?

This trial is for adults with a specific type of lung cancer (non-squamous NSCLC) that can be surgically removed. Patients must have certain EGFR mutations, good performance status, and no history of severe lung conditions or other cancers within the last 2 years. Prior cancer treatments for NSCLC are not allowed.

What is being tested?

The study tests Osimertinib alone or combined with chemotherapy against standard-of-care chemotherapy in patients who can undergo surgery to remove their lung cancer. It's a Phase III trial where participants are randomly assigned to one of three groups.

What are the potential side effects?

Osimertinib may cause diarrhea, rash, dry skin, nail changes, mouth sores; while chemotherapy drugs like Cisplatin and Carboplatin can lead to nausea, vomiting, hair loss and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My non-squamous NSCLC is at stage II - IIIB N2 and can be completely removed with surgery.

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My lung cancer can be fully removed by surgery, as confirmed by a specialized team.

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My tumor has EGFR mutations sensitive to specific treatments.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had lung inflammation or damage that needed steroids.

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My lung cancer is a mix of small cell and non-small cell types.

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My cancer has spread to major organs or large lymph nodes.

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I have not had any systemic anti-cancer treatments for my lung cancer.

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My lung cancer is at an early or advanced stage, but not the final stage.

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I am scheduled for radiotherapy before surgery as part of my treatment.

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I have been treated with EGFR-TKI therapy before.

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I am a candidate for a minor lung surgery.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization to an average of 12 weeks after the first dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization to an average of 12 weeks after the first dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization to an average of 12 weeks after the first dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Major Pathological Response (MPR)

Secondary study objectives

Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items)

Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items)

Disease free survival (DFS)

+4 more

Other study objectives

Cure rate

Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone

Side effects data

From 2020 Phase 4 trial • 60 Patients • NCT03853551

10%

Blood creatine phosphokinase increased

10%

Fatigue

Decreased appetite

Diarrhoea

Cough

Mucosal inflammation

Rash

Pain in extremity

Constipation

Thrombocytopenia

Paronychia

Dyspnoea

Dengue fever

Disease progression

Cardio-respiratory arrest

Cataract

Mouth Ulceration

Deep Vein Thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

Single Arm

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Arm 3: Osimertinib monotherapyExperimental Treatment1 Intervention

Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)

Group II: Arm 2: Osimertinib with platinum-based chemotherapyExperimental Treatment4 Interventions

Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)

Group III: Arm 1: Placebo with platinum-based chemotherapyPlacebo Group4 Interventions

Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pemetrexed

2014

Completed Phase 3

~5550

Carboplatin

2014

Completed Phase 3

~6120

Cisplatin

2013

Completed Phase 3

~3120

Osimertinib

2017

Completed Phase 4

~1100

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include EGFR Tyrosine Kinase Inhibitors (TKIs) like Osimertinib, chemotherapy, and immunotherapy. Osimertinib works by selectively inhibiting the epidermal growth factor receptor (EGFR) with activating mutations, which are often present in NSCLC, thereby blocking the signaling pathways that promote cancer cell proliferation and survival. Chemotherapy targets rapidly dividing cells, including cancer cells, by interfering with their DNA replication and cell division processes. Immunotherapy, such as anti-PD-1 or anti-PD-L1 antibodies, enhances the body's immune response against cancer cells by blocking the proteins that inhibit immune cell activity. These treatments are crucial for NSCLC patients as they offer targeted and effective options to manage and potentially improve survival outcomes.

Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Mutation: First Line Treatment and Beyond.