What side effects are associated with this type of intervention?

Osimertinib, an EGFR Tyrosine Kinase Inhibitor used in NSCLC, commonly causes side effects such as diarrhea, rash, dry skin, and nail toxicity. Other EGFR TKIs may have similar side effects. Chemotherapy, often used in combination with TKIs, can lead to nausea, vomiting, fatigue, hair loss, and increased risk of infection due to bone marrow suppression. Immunotherapy, another common treatment, can cause immune-related adverse effects like colitis, pneumonitis, hepatitis, and endocrinopathies. Each treatment has a unique side effect profile, and patients should discuss these with their healthcare provider to manage and mitigate these effects effectively.

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 target similar pathways. Additionally, immunotherapies such as Pembrolizumab and Nivolumab have been approved for NSCLC, often in combination with chemotherapy, to enhance treatment efficacy. These therapies represent significant advancements in the targeted treatment of NSCLC, particularly for patients with specific genetic mutations or protein expressions.

What other types of research exist?

Promising novel alternatives to Osimertinib for NSCLC patients include: 1) Amivantamab, a bispecific antibody targeting EGFR and MET, which has shown efficacy in patients with EGFR exon 20 insertion mutations. 2) Mobocertinib, an oral EGFR tyrosine kinase inhibitor specifically targeting EGFR exon 20 insertion mutations. 3) Combination therapies such as Pembrolizumab plus chemotherapy (platinum-doublet) have also shown improved outcomes in advanced NSCLC. These alternatives offer new avenues for treatment, particularly for patients with specific genetic mutations or those who have progressed on first-line therapies.

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Chemotherapy + Osimertinib for Non-Small Cell Lung Cancer (COMPEL Trial)

Phase 3

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling criteria at screening.

World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.

Must not have

Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib.

Mean resting QTc >470 msec or any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram or any factors that increase the risk of QTc prolongation or risk of arrhythmic events.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomization through post progression survival follow-up (up to approximately 3 years)

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Osimertinib may cause side effects such as diarrhea, rashes, dry skin; nail changes; mouth sores; reduced appetite; fatigue; cough and shortness of breath. Chemotherapy can lead to hair loss, nausea/vomiting, increased risk of infection due to low blood cell counts.

Eligibility Criteria

Inclusion Criteria

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

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

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

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

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My lung cancer is non-squamous and confirmed by a lab test.

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My cancer outside the brain worsened after initial improvement or stability with osimertinib treatment.

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I have at least one cancer lesion that has not been treated with radiation.

Exclusion Criteria

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

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

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My heart's electrical activity is normal and doesn't pose a risk for irregular rhythms.

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

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I am not in a clinical trial with drugs other than osimertinib.

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

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I have had lung inflammation that needed steroid treatment.

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I am not taking any strong CYP3A4 inducers.

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I have no lasting side effects from previous treatments.

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I haven't had extensive radiation to my bone marrow or wide field radiation in the last 4 weeks.

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I have received treatment for cancer that affects my whole body.

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My brain cancer has worsened despite first-line osimertinib treatment.

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I cannot tolerate the standard 80 mg dose of osimertinib.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization through post progression survival follow-up (up to approximately 3 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization through post progression survival follow-up (up to approximately 3 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization through post progression survival follow-up (up to approximately 3 years) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression free survival(PFS):time from randomization until progression(intra- or extracranial whichever occurs first)per RECIST 1.1(for extracranial)and CNS RECIST 1.1(for intracranial progression)as assessed by Investigator or death due to any cause

Secondary study objectives

Extracranial PFS is defined as time from randomization until extracranial progression per RECIST 1.1 as assessed by the Investigator at local site or death due to any cause

Intracranial PFS is defined as time from randomization until intracranial progression per CNS RECIST 1.1 as assessed by the Investigator at local site or death due to any cause

Number of patients with serious and non-serious adverse events

+1 more

Awards & Highlights

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Treatment Arm AExperimental Treatment1 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 BPlacebo Group1 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

0 / 18Eligibility 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 specifically targeting and inhibiting the epidermal growth factor receptor (EGFR) mutations that drive cancer cell growth and proliferation, making it highly effective for patients with these mutations. Chemotherapy, on the other hand, uses cytotoxic drugs to kill rapidly dividing cancer cells, though it affects both cancerous and healthy cells. Immunotherapy, such as anti-PD-1 or anti-PD-L1 therapies, enhances the body's immune system to recognize and attack cancer cells. These treatments are crucial for NSCLC patients as they offer targeted and systemic approaches to control and potentially eradicate the cancer, improving survival rates and quality of life.

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