Osimertinib for Lung Cancer

(NEOLA Trial)

Not currently recruiting at 65 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Antivirals

Must not be taking: CYP3A4 inducers

Disqualifiers: Small cell histology, ILD, uncontrolled diseases, 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

Compensation: Varies

Number of Visits: 17

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for individuals with Stage III non-small cell lung cancer (NSCLC) that cannot be surgically removed. Researchers aim to evaluate the effectiveness of the drug osimertinib when administered before and after radiation and chemotherapy. The trial will assess a combination of drugs, including cisplatin or carboplatin (types of chemotherapy drugs), alongside radiation. Individuals with NSCLC who have specific EGFR gene mutations and have not previously received chemotherapy or radiation may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires participants to avoid medications or supplements that strongly induce CYP3A4, a liver enzyme, at least 3 weeks before starting the study. If you're taking such medications, you may need to stop or switch them.

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

Research shows that osimertinib is generally well-tolerated for treating non-small cell lung cancer (NSCLC). Studies have found it provides strong survival benefits while keeping side effects manageable. Most patients experience side effects like rash, diarrhea, and nausea, which are usually mild to moderate.

Osimertinib is already approved for use in other stages of NSCLC, indicating its safety and effectiveness. When combined with chemotherapy, osimertinib has shown consistent benefits without unexpected safety issues.

This trial also includes chemotherapy drugs such as cisplatin or carboplatin, and pemetrexed or paclitaxel. These drugs are common in cancer treatment, and their side effects, like low blood cell counts, fatigue, and nausea, are well-known. Supportive care usually manages these side effects.

Overall, current evidence suggests that the treatments in this trial are generally safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Osimertinib is unique because it specifically targets mutations in the EGFR (epidermal growth factor receptor) that are often found in lung cancer. This makes it different from traditional chemotherapy options like Cisplatin or Carboplatin combined with Pemetrexed or Paclitaxel, which work by killing rapidly dividing cells but don't target specific mutations. Researchers are excited about osimertinib because it offers a more personalized treatment approach and has shown promise in delaying disease progression with potentially fewer side effects. By targeting the genetic drivers of the cancer, osimertinib could provide better outcomes for patients with EGFR-mutated lung cancer.

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

Studies have shown that osimertinib effectively treats non-small cell lung cancer (NSCLC), particularly in patients with specific EGFR gene mutations. In this trial, participants will receive open-label osimertinib induction treatment, followed by combined chemotherapy and radiation therapy (CRT). Research indicates that when osimertinib follows combined chemotherapy and radiation, 84% of patients with Stage III EGFR-mutated NSCLC survive after three years. Other studies have demonstrated that osimertinib helps patients live longer and is generally well-tolerated. It also serves as an effective second treatment option for those who did not respond well to their first treatment. Overall, osimertinib continues to show promise as a key treatment for EGFR-mutated lung cancer at different stages. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with Stage III, unresectable non-small cell lung cancer (NSCLC) that have common EGFR mutations. Participants should not have had prior treatment for this stage of cancer.

Inclusion Criteria

Minimum life expectancy of > 12 weeks at Day 1.

My tumor has EGFR mutations sensitive to certain treatments.

My lung cancer is advanced (Stage III) and cannot be removed by surgery.

Exclusion Criteria

Patients should refrain from breastfeeding from enrolment throughout the study and until 6 weeks after last dose of study intervention.

Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks (unless the safety profile is known prior to first dose of study intervention), or concurrent enrolment in another clinical study (unless the study is observational [noninterventional], or the patient is in the followup period of an interventional study).

Previous enrolment in the present study. Rescreening of individuals who were screen failures is allowed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive open-label osimertinib induction treatment

8 weeks

Visits every 2 to 4 weeks

CRT Treatment

Participants undergo CRT treatment, including chemotherapy and radiation therapy

6 weeks

Chemotherapy every 3 weeks, daily visits for radiation therapy

Maintenance Treatment

Participants receive osimertinib maintenance treatment until progression or death

Visits every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin or Carboplatin; Pemetrexed or Paclitaxel
• Osimertinib
• Radiation

Trial Overview The study tests the effectiveness and safety of osimertinib given before and after standard chemotherapy and radiation therapy (CRT) in treating NSCLC. Osimertinib is administered as an induction therapy followed by maintenance post-CRT.

How Is the Trial Designed?

Group I: Open-Label Osimertinib Induction Treatment Experimental Treatment 3 Interventions

Patients will receive open-label osimertinib induction treatment for 8 weeks (± 1 week window to account for patient variability and CRT scheduling), followed by CRT treatment for 6 weeks (± 1 week) and then osimertinib maintenance treatment until RECIST 1.1-defined radiological progression by investigator unless there is evidence of unacceptable toxicity or if the patient requests to stop the study treatment.

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

Cisplatin combined with other agents like vinblastine or etoposide shows promise as an effective pre-radiotherapy treatment for locally advanced non-small cell lung cancer (NSCLC), but optimal scheduling is still being researched.

In a study of 170 patients, concurrent chemotherapy with carboplatin and radiation led to increased toxicity, including significantly higher rates of neutropenia and thrombocytopenia, indicating that while this approach may improve treatment efficacy, it also raises safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. Bishop, JF.[2019]

The study demonstrated that three cycles of full-dose cisplatin and pemetrexed can be safely administered alongside definitive thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer, with dose-limiting toxicities not exceeding 33%.

With a median follow-up of 22 months, the 24-month survival rate was 57.5%, indicating promising efficacy of this treatment regimen for improving survival in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent chemoradiation with pemetrexed and cisplatin followed by consolidation pemetrexed for patients with unresectable stage III non-small cell lung cancer. Cardenal, F., Arnaiz, MD., Morán, T., et al.[2015]

In a randomized phase 2 trial involving 101 patients with stage IV lung adenocarcinoma, the combination of Pemetrexed and Cisplatin (Pem-Cis) showed a significantly higher one-year survival rate of 72.0% compared to 52.9% for Docetaxel and Cisplatin (Doc-Cis).

Patients receiving Pem-Cis also experienced longer progression-free survival (12.6 months) compared to those on Doc-Cis (7.5 months), indicating that Pem-Cis may be a more effective first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. Su, SF., Li, M., Geng, YC., et al.[2020]

The combination of carboplatin and dose-dense pemetrexed with involved field radiotherapy is feasible for treating locally advanced and oligometastatic non-small cell lung cancer (NSCLC), as shown in a phase I study with 18 enrolled patients.

Despite some dose-limiting toxicities observed, the treatment resulted in a median survival time of 28.6 months, with 13 out of 16 evaluable patients showing a local regional response, indicating promising efficacy for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. Shen, X., Denittis, A., Werner-Wasik, M., et al.[2021]

Preclinical and clinical trials indicate that platinum compounds, like cisplatin, can enhance the effectiveness of radiation therapy in treating locally advanced non-small cell lung cancer, with acceptable levels of toxicity reported.

Phase III trials have shown that using cisplatin alongside radiation is effective compared to radiation alone, suggesting that this combination could be a promising treatment strategy for patients with unresectable tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of stage III non-small cell lung cancer with thoracic radiation therapy and simultaneous platinum chemotherapy. Bonomi, P.[2013]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

Combined chemotherapy and radiation therapy is more effective than radiation therapy alone for treating unresectable non-small cell lung cancer, although the best timing for chemotherapy (concurrent vs. sequential) is still uncertain.

In patients with stage IIIa and IIIb disease, surgery after neoadjuvant chemotherapy and radiation therapy shows comparable resectability and survival rates, but the impact of surgery on overall survival remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current management of unresectable non-small cell lung cancer. Livingston, RB.[2018]

In a retrospective study of 16 patients with metastatic NSCLC treated with osimertinib and thoracic radiation therapy (TRT), 56% experienced severe pneumonitis (grade 2 or higher), indicating a significant risk associated with this combination treatment.

The majority of patients with severe pneumonitis (grade 3 or higher) had tumors located near the proximal bronchial tree, suggesting that tumor location may influence the risk of developing this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Severe Pneumonitis After Combined Thoracic Radiotherapy and Osimertinib. Smith, CP., Xiang, M., Yoon, SM., et al.[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, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., 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]

In a study of 47 patients with advanced non-small cell lung cancer (NSCLC) who had EGFR mutations, those who received osimertinib immediately after nivolumab treatment experienced a significantly higher rate of severe liver toxicity (57.1%) compared to those treated with other drugs before osimertinib (5.0%).

The findings suggest that administering osimertinib right after immune checkpoint inhibitors like nivolumab may increase the risk of serious adverse events, particularly hepatotoxicity, highlighting the need for careful treatment sequencing in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non-small cell lung cancer harboring EGFR mutation. Yamaguchi, O., Kaira, K., Kawasaki, T., et al.[2022]

Citations

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Tagrisso plus chemotherapy demonstrated a median ... Over the past decade, Tagrisso has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung ...

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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. nejm.org nejm.org/doi/full/10.1056/NEJMoa2402614

Osimertinib after Chemoradiotherapy in Stage III EGFR- ... Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% ...

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New study results reinforce TAGRISSO® (osimertinib) as ... In LAURA Phase III trial, TAGRISSO continues to demonstrate improved overall survival trend in unresectable, Stage III setting.

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Updated Overall Survival Data (OSI-FACT-OS) This study supports the long-term efficacy of OSI, with PFS and OS comparable to those in the FLAURA trial in a Japanese real-world setting.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730425001299

Osimertinib as First-Line Treatment for Patients With ... This study supports the long-term efficacy of OSI, with PFS and OS comparable to those in the FLAURA trial in a Japanese real-world setting.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38828959/

Phase II Efficacy and Safety of 80 mg Osimertinib in ... The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs.

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Osimertinib with or without Chemotherapy in EGFR- ... CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3).