Osimertinib After Chemoradiation for Lung Cancer

(LAURA Trial)

Recruiting at 105 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: EGFR-TKI, CYP3A4 inducers

Disqualifiers: Mixed histology, ILD, pneumonitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 16

Duration: Up to 63 months

216 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests osimertinib, a medication for certain lung cancers, in patients with stage III unresectable NSCLC who have specific EGFR mutations. Osimertinib aims to slow or stop cancer growth by blocking a protein involved in cancer cell growth.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications or herbal supplements known to be strong inducers of CYP3A4 at least 3 weeks before starting the study treatment.

What data supports the effectiveness of the drug Osimertinib for lung cancer?

Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific genetic mutations, particularly the EGFR T790M mutation, by significantly prolonging disease-free survival in patients with early-stage cancer and those who have developed resistance to other treatments. ^{1 2 3 4 5}

Is osimertinib generally safe for humans?

Osimertinib has been studied in various trials for lung cancer, and common side effects include diarrhea, rash, dry skin, and nail issues. Serious side effects occurred in about 28% of patients, and 5.6% stopped treatment due to these effects, but it is generally considered to have a manageable safety profile. ^{1 2 3 6 7}

How is the drug osimertinib unique for lung cancer treatment?

Osimertinib is unique because it is an oral medication specifically designed to target and inhibit mutations in the epidermal growth factor receptor (EGFR) that are resistant to previous treatments, particularly the T790M mutation in non-small cell lung cancer (NSCLC). This makes it effective for patients who have developed resistance to earlier EGFR-targeted therapies. ^{1 3 4 5 8}

Research Team

Shun Lu

Principal Investigator

Shanghai Chest Hospital, Shanghai, China

Suresh S Ramalingam, MD

Principal Investigator

Emory University School of Medicine, Atlanta, U.S.

Eligibility Criteria

This trial is for adults with stage III unresectable non-small cell lung cancer that has specific EGFR mutations and hasn't worsened after chemoradiation. Participants need a WHO performance status of 0 or 1, must use contraception if necessary, and have completed chemoradiation within the past 6 weeks. Exclusions include prior NSCLC treatments other than for stage III, inability to absorb the drug due to gastrointestinal issues, certain heart risks, uncontrolled diseases like hypertension, or severe systemic diseases.

Inclusion Criteria

My tumor has a specific EGFR mutation known to respond to certain treatments.

I've had chemoradiation for cancer, including platinum-based chemo and specific radiation doses.

My cancer did not worsen after receiving platinum-based chemoradiation.

Exclusion Criteria

I have severe nausea, vomiting, or gut issues that make it hard for me to take pills.

I have lung inflammation symptoms after chemoradiation.

Your heart's electrical activity is too high, which can be measured by a heart test called an ECG.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants receive definitive platinum-based chemoradiation therapy

6 weeks

Treatment

Participants receive osimertinib or placebo until disease progression or unacceptable toxicity

Up to 63 months

Every 8 weeks for first 48 weeks, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 63 months

Every 8 weeks for first 48 weeks, then every 12 weeks

Open-label extension

Participants may receive open-label osimertinib after progression if they are deriving clinical benefit

Treatment Details

Interventions

• Osimertinib

Trial Overview The LAURA study tests the effectiveness and safety of Osimertinib following chemoradiation therapy compared to a placebo in patients with a particular mutation-positive lung cancer. It's designed to see if this treatment can improve outcomes for these patients after initial therapy.

Participant Groups

Group I: Osimertinib Experimental Treatment 1 Intervention

Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule.

Group II: Placebo Osimertinib Placebo Group 1 Intervention

Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

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 (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]

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]

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 phase 3 trial involving 556 patients with advanced non-small-cell lung cancer (NSCLC), osimertinib demonstrated significantly longer progression-free survival (18.9 months) compared to standard EGFR-TKIs (10.2 months), indicating its superior efficacy as a first-line treatment.

Osimertinib also had a similar safety profile to standard EGFR-TKIs but resulted in fewer serious adverse events (34% vs. 45%), making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. Soria, JC., Ohe, Y., Vansteenkiste, J., et al.[2022]

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 (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]

In a phase 2 study involving 210 patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), osimertinib demonstrated significant efficacy, with 70% of patients achieving an objective response, including 3% with complete responses.

Osimertinib was found to have manageable side effects, although serious adverse events occurred in 25% of patients, with interstitial lung disease being the only fatal event possibly related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Goss, G., Tsai, CM., Shepherd, FA., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. France pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. [2022]