Osimertinib After Chemoradiation for Lung Cancer

(LAURA Trial)

Not currently recruiting at 140 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of osimertinib, a medication for people with a specific type of lung cancer. It targets individuals with stage III non-small cell lung cancer that cannot be surgically removed and who have an EGFR mutation. Participants should have recently completed chemoradiation therapy without cancer progression. The trial involves taking osimertinib daily and comparing it to a placebo to determine its effectiveness in managing the condition. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that osimertinib is likely to be safe for humans?

Research has shown that patients generally tolerate osimertinib well. It is already approved for treating certain types of lung cancer, indicating it has passed extensive safety tests for those conditions. Most people taking osimertinib experience mild to moderate side effects, such as diarrhea and skin rash. However, rare reports of serious side effects, like lung inflammation, have occurred. Despite these rare events, the benefits of the treatment often outweigh the risks for people with specific genetic markers in their cancer. Consulting a healthcare provider is important to determine if this treatment is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Osimertinib is unique because it specifically targets a mutation in the EGFR gene, which is often responsible for driving the growth of certain lung cancers. Unlike traditional chemotherapies that attack rapidly dividing cells indiscriminately, osimertinib zeroes in on this mutation, potentially leading to fewer side effects and more effective treatment for patients with this specific genetic profile. Researchers are excited about osimertinib because it represents a targeted therapy approach, offering hope for better outcomes in patients with EGFR-mutated lung cancer, especially after undergoing chemoradiation.

What evidence suggests that osimertinib could be an effective treatment for lung cancer?

Research has shown that osimertinib effectively treats non-small cell lung cancer (NSCLC) with specific genetic changes known as EGFR mutations. One study found that patients taking osimertinib experienced a longer period before their cancer worsened compared to those on older treatments. Another study demonstrated that combining osimertinib with chemotherapy led to even better results than using osimertinib alone. Additionally, real-world studies have confirmed its effectiveness in patients when other treatments fail. In this trial, participants will receive either osimertinib or a placebo to evaluate its effectiveness after chemoradiation. Overall, osimertinib is a strong option for treating EGFR-positive lung cancer. ^{3 6 7 8 9}

Who Is on the 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.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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 (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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39118879/

Real-world efficacy of low dose osimertinib as second-line ... Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2306434

Osimertinib with or without Chemotherapy in EGFR- ... First-line treatment with osimertinib–chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S246829422500036X

Real-world comparative outcomes of EGFR-TKIs for first- ... This study compared real-world clinical outcomes of 1L osimertinib versus 1st or 2nd generation EGFR-TKIs (1/2G-TKIs) in patients with EGFR+ mNSCLC.

4. jtocrr.org jtocrr.org/article/S2666-3643(24)00090-0/fulltext

The Whole Picture of First-Line Osimertinib for EGFR ... A total of 583 patients received osimertinib. The median progression-free and overall survival were 20.0 (95% confidence interval [CI]: 17.6– ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37840304/

Exploring the impact of patient-specific clinical features on ... Limited data exists on the impact of patient characteristics or osimertinib exposure on effectiveness outcomes. This was a Dutch, multicenter ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4940973/

The safety and efficacy of osimertinib for the ... - PubMed Central We review the rapid clinical development and approval of the third-generation EGFR TKI osimertinib for treatment of NSCLCs with EGFR-T790M.

7. tagrisso.com tagrisso.com/late-stage-egfr-nsclc.html

Treatment for Late-Stage EGFR+ NSCLC TAGRISSO is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC) that has certain abnormal epidermal growth factor receptor ( ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11356521/

Adverse Events in Osimertinib Treatment for EGFR ... This article delves into the exploration of adverse events linked to osimertinib, shedding light on a rare yet life-threatening occurrence: severe ...

9. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/tagrisso-us-approval-in-unresectable-lung-cancer.html

Tagrisso approved in the US for patients with unresectable ... Based on LAURA Phase III trial results which showed Tagrisso extended median progression-free survival by more than three years.