Chemotherapy + Osimertinib for Non-Small Cell Lung Cancer

(COMPEL Trial)

Recruiting at 44 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Osimertinib

Must not be taking: CYP3A4 inducers

Disqualifiers: CNS progression, ILD, uncontrolled diseases, 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

Compensation: Varies

Number of Visits: 11

Duration: 12 weeks

98 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of chemotherapy and osimertinib in patients with advanced lung cancer that has spread outside the brain after earlier treatment. Osimertinib blocks a protein that helps cancer grow, and chemotherapy kills cancer cells. Osimertinib has shown improvements in progression-free survival over earlier treatments and is preferred for initial treatment of EGFR-mutant NSCLC.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using medications or supplements that strongly affect a specific liver enzyme (CYP3A4). It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of chemotherapy and osimertinib for non-small cell lung cancer?

Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific genetic mutations, significantly prolonging progression-free survival and demonstrating durable tumor response rates in clinical trials. It is particularly effective for patients with EGFR T790M mutation-positive NSCLC who have developed resistance to earlier treatments. ^{1 2 3 4 5}

Is the combination of chemotherapy and osimertinib safe for humans?

Osimertinib, also known as Tagrisso, has been studied for safety in patients with non-small cell lung cancer. Common side effects include diarrhea, rash, dry skin, and nail issues, with some patients experiencing more severe side effects. It is generally well tolerated, but some patients may need to stop treatment due to side effects. ^{1 2 3 4 6}

How does the drug combination of Chemotherapy and Osimertinib differ from other drugs for non-small cell lung cancer?

The combination of Chemotherapy and Osimertinib is unique because it pairs traditional chemotherapy, which kills rapidly dividing cancer cells, with Osimertinib, a targeted therapy that specifically inhibits a protein involved in cancer cell growth. This dual approach aims to enhance treatment effectiveness by attacking the cancer in two different ways. ^{7 8 9 10 11}

Eligibility Criteria

This trial is for adults with advanced or metastatic non-squamous NSCLC who've seen their cancer progress after first-line osimertinib treatment. They should be in good physical condition, not planning to have surgery or radiotherapy, and willing to use effective contraception. People can't join if they've had certain treatments recently, have heart rhythm problems, severe diseases, another active cancer within 2 years, lung conditions like ILD/pneumonitis, or can't absorb the drug well.

Inclusion Criteria

I am not pregnant and use effective birth control or cannot become pregnant.

I am fully active or restricted in physically strenuous activity but can do light work.

My lung cancer is advanced, cannot be cured with surgery or radiotherapy.

Exclusion Criteria

I cannot take osimertinib due to severe nausea, vomiting, gut diseases, swallowing issues, or major bowel surgery.

I haven't had treatment for another cancer within the last 2 years.

I have not had major surgery in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive platinum plus pemetrexed chemotherapy with either osimertinib or placebo for 4 cycles, followed by maintenance therapy

12 weeks

4 visits (in-person) for initial cycles, then maintenance visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 6 weeks for the first 13 cycles, then every 12 weeks

Treatment Details

Interventions

• Chemotherapy
• Osimertinib

Trial Overview The study tests if adding osimertinib to chemotherapy is better than adding a placebo (a substance with no therapeutic effect) for NSCLC patients whose disease progressed after initial osimertinib therapy. Participants will receive either the combination of chemotherapy plus osimertinib or chemotherapy plus placebo.

Participant Groups

Group I: Treatment Arm A Experimental Treatment 1 Intervention

All randomized patients will receive osimertinib 80 mg QD with pemetrexed (500 mg/m\^2) (with pre-treatment) plus either cisplatin (75 mg/m\^2) or carboplatin (\[AUC\] 5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg QD plus pemetrexed maintenance (500 mg/m\^2) on Day 1 of 21-day cycles

Group II: Treatment Arm B Placebo Group 1 Intervention

All randomized patients will receive placebo QD with pemetrexed (500 mg/m\^2) (with pre-treatment) plus either cisplatin (75 mg/m\^2) or carboplatin (AUC5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by placebo QD plus pemetrexed maintenance (500 mg/m\^2) on Day 1 of 21-day cycles

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

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]

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) 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 is a third-generation EGFR tyrosine kinase inhibitor that effectively targets specific mutations in advanced non-small cell lung cancer (NSCLC), including the T790M mutation, leading to significantly longer progression-free survival compared to first-generation EGFR TKIs like erlotinib or gefitinib.

The benefits of osimertinib in prolonging progression-free survival were consistent across all patient groups, regardless of the type of EGFR mutation or the presence of CNS metastases, and it has a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. Scott, LJ.[2020]

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]

Lung cancer is the leading cause of cancer-related deaths in Europe and North America, with non-small cell lung cancer (NSCLC) making up 70-80% of cases, and current chemotherapy treatments show limited effectiveness with overall response rates below 20%.

The Southern Italy Cooperative Oncology Group is exploring new triplet chemotherapy combinations involving cisplatin and two additional agents, aiming to improve patient outcomes in advanced NSCLC, with ongoing phase I, II, and III trials evaluating the safety and efficacy of these new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. Frasci, G., Panza, N., Comella, G., et al.[2022]

Chemotherapy, particularly with platinum-based drugs like cisplatin and carboplatin, is a standard treatment for patients with locally advanced or metastatic non-small-cell lung cancer, showing a beneficial survival effect confirmed by clinical studies.

Research is ongoing into new platinum agents, such as BBR3464 and ZD0473, which may offer alternatives to existing treatments and could be combined with other drugs to improve outcomes for patients with advanced or resistant solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum drugs in the treatment of non-small-cell lung cancer. Cosaert, J., Quoix, E.[2023]

Less than 25% of patients with non-small cell lung cancer (NSCLC) have early-stage disease that can be surgically removed, highlighting the need for effective treatments for advanced stages.

Cisplatin-based chemotherapy, especially in combination with newer agents like gemcitabine and paclitaxel, has shown improved survival rates and response rates exceeding 35% in advanced NSCLC, indicating its efficacy in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on European randomized studies in non-small cell lung cancer. Giaccone, G., Manegold, C., Rosell, R., et al.[2007]

A variety of new agents, including taxanes, gemcitabine, and irinotecan, have shown promise in early clinical studies for treating non-small-cell lung cancer (NSCLC), indicating potential for improved treatment options.

Cisplatin remains a key component in combination therapies for NSCLC, being tested alongside these new agents, radiation, and surgery in numerous trials to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in metastatic non-small-cell lung cancer. Sandler, A.[2022]

References

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

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

2. France pubmed.ncbi.nlm.nih.gov

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

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

Osimertinib: First Global Approval. [2022]

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

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

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

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. [2020]

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

New Adjuvant Drug for Lung Cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Three emerging new drugs for NSCLC: pemetrexed, bortezomib, and cetuximab. [2022]

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

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Platinum drugs in the treatment of non-small-cell lung cancer. [2023]

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

An update on European randomized studies in non-small cell lung cancer. [2007]

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

Chemotherapy in metastatic non-small-cell lung cancer. [2022]