A Study to Evaluate Chemotherapy Plus Osimertinib Against Chemotherapy Plus Placebo in Patients With Non-small Cell Lung Cancer (NSCLC)
COMPEL
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Pemetrexed Chemotherapy Plus Osimertinib Versus Platinum Plus Pemetrexed Chemotherapy Plus Placebo in Patients With EGFRm, Locally Advanced or Metastatic NSCLC Who Have Progressed Extracranially Following First-Line Osimertinib Therapy (COMPEL)
2 other identifiers
interventional
98
6 countries
40
Brief Summary
The study will evaluate the efficacy and safety of treatment with chemotherapy in combination with osimertinib compared to chemotherapy in combination with placebo in patients whose disease has progressed extracranially following first-line osimertinib treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3 nonsmall-cell-lung-cancer
Started Sep 2021
Typical duration for phase_3 nonsmall-cell-lung-cancer
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 11, 2021
CompletedFirst Posted
Study publicly available on registry
February 21, 2021
CompletedStudy Start
First participant enrolled
September 12, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 28, 2024
CompletedResults Posted
Study results publicly available
January 13, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
June 2, 2027
ExpectedApril 21, 2026
March 1, 2026
3.1 years
February 11, 2021
October 8, 2025
March 31, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
Progression free survival is defined as time from randomization until progression (intracranial or extracranial, whichever occurs first) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for extracranial progression) and Central nervous system (CNS) RECIST 1.1 (for intracranial progression) as assessed by the Investigator at local site or death due to any cause.
From date of first dose (Day 1) until date of progression at local site or death due to any cause or data cut-off date whichever occurred first (up to 3 years 1 month)
Secondary Outcomes (4)
Intracranial Progression Free Survival in Participants With Brain Metastases at Baseline
Assessed from date of first dose (Day 1) until date of intracranial progression at local site or death due to any cause or data cut off date whichever occurred first (up to 3 years 1 month), data for 6 months reported
Intracranial Progression Free Survival in Participants Without Brain Metastases at Baseline
Assessed from date of first dose (Day 1) until date of intracranial progression at local site or death due to any cause or data cut off date whichever occurred first (up to 3 years 1 month), data for 6 months reported
Extracranial Progression Free-survival
From date of first dose (Day 1) until date of extracranial progression at local site or death due to any cause or data cut-off date whichever occurred first (up to 3 years 1 month)
Overall Survival (OS)
From date of first dose (Day 1) until post progression survival follow-up (up to 3 years 1 month)
Study Arms (2)
Treatment Arm A
EXPERIMENTALAll 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
Treatment Arm B
PLACEBO COMPARATORAll 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
Interventions
Randomized patients will receive oral dose of osimertinib with intravenous (IV) pemetrexed plus either IV cisplatin or IV carboplatin
Randomized patients will receive oral dose of placebo matching osimertinib with IV pemetrexed plus either IV cisplatin or IV carboplatin
Eligibility Criteria
You may qualify if:
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
- Pathologically confirmed non-squamous NSCLC.
- Locally advanced (clinical stage IIIB or IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC, not amenable to curative surgery or radiotherapy.
- Evidence of radiological extracranial disease progression following (Investigator-assessed) response or SD for ≥ 6 months during first-line osimertinib treatment, but who have not received further, subsequent treatment.
- Tumor known to harbor 1 of the 2 or both common epidermal growth factor receptor (EGFR) mutations known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M.
- World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.
- Life expectancy \>12 weeks at Day 1.
- At least 1 lesion, not previously irradiated, that can be accurately measured.
- 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.
- Male patients must be willing to use barrier contraception
You may not qualify if:
- Clinical or radiological evidence of CNS progression on first-line osimertinib.
- Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis.
- Any evidence of severe or uncontrolled systemic diseases.
- Any of the following cardiac criteria:
- i) Mean resting QTc \>470 msec ii) Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram iii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
- Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of investigational product (IP).
- Any unresolved toxicities from prior therapy.
- 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.
- More than 4 weeks elapsed since last dose of osimertinib by date of randomization.
- Unable to tolerate osimertinib 80 mg first-line therapy.
- Prior treatment with any systemic anti-cancer therapy.
- Major surgery within 4 weeks of the first dose of IP.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP.
- Current use of medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4.
- Participation in another clinical study with an IP other than first-line osimertinib during the 4 weeks prior to Day 1.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Parexelcollaborator
Study Sites (40)
Research Site
Silver Spring, Maryland, 20910, United States
Research Site
Boston, Massachusetts, 02114, United States
Research Site
Beijing, 100005, China
Research Site
Beijing, 100142, China
Research Site
Ganzhou, 341099, China
Research Site
Guangzhou, 510080, China
Research Site
Jinan, 250013, China
Research Site
Shenyang, 110001, China
Research Site
Tianjin, 300060, China
Research Site
Zhengzhou, 450008, China
Research Site
Berlin, 12351, Germany
Research Site
Cologne, 50937, Germany
Research Site
Cologne, 51109, Germany
Research Site
Hanover, 30625, Germany
Research Site
München, D-80336, Germany
Research Site
Beersheba, 84101, Israel
Research Site
Jerusalem, 9103102, Israel
Research Site
Jerusalem, 9112001, Israel
Research Site
Kfar Saba, 4428164, Israel
Research Site
Tel Aviv, 6423906, Israel
Research Site
Tel Litwinsky, 52621, Israel
Research Site
Florence, 50134, Italy
Research Site
Meldola, 47014, Italy
Research Site
Messina, 98158, Italy
Research Site
Naples, 80131, Italy
Research Site
Padova, 35128, Italy
Research Site
Roma, 00168, Italy
Research Site
Terni, 05100, Italy
Research Site
Verona, 37124, Italy
Research Site
Alicante, 03010, Spain
Research Site
Barcelona, 08907, Spain
Research Site
Córdoba, 14004, Spain
Research Site
León, 24071, Spain
Research Site
Madrid, 28040, Spain
Research Site
Málaga, 29010, Spain
Research Site
Murcia, 30008, Spain
Research Site
Oviedo, 33011, Spain
Research Site
Palma de Mallorca, 07010, Spain
Research Site
Seville, 41013, Spain
Research Site
Valencia, 46010, Spain
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- The patient, the Investigator, the study team (Sponsor, Contract research organization) and the study site staff will be blinded to osimertinib or placebo allocation. Patients may participate in the open label part of trial at the discretion of the investigator to receive osimertinib and continue any ongoing chemotherapy if intracranial progression is their first progression event.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2021
First Posted
February 21, 2021
Study Start
September 12, 2021
Primary Completion
October 28, 2024
Study Completion (Estimated)
June 2, 2027
Last Updated
April 21, 2026
Results First Posted
January 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.