Non Small Cell Lung CancerPhase 2FLAMENCT04769388
Osimertinib Plus Chemotherapy vs Osimertinib in EGFRm NSCLC With Persistence Week-3 ctDNA EGFRm After 1L Osimertinib
A Phase 2 study testing Osimertinib and Pemetrexed/Carboplatin in people with Non Small Cell Lung Cancer, run by Beijing Cancer Prevention & Treatment Society at 1 site in China.
Trial summary
This is a prospective, randomised, open-label, positive-controlled study to investigate the efficacy and safety of Osimertinib plus Carboplatin/Pemetrexed versus Osimertinib monotherapy in locally advanced or metastatic EGFRm NSCLC patients with EGFRm persistence in ctDNA at 3 weeks after first-line therapy with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Osimertinib and Pemetrexed/Carboplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 7 Feb 2022to 26 Jan 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision and signed of informed consent prior to any study specific procedures;
- Male or female, aged at least 18 years;
- Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1;
- Newly diagnosed, and histologically documented locally advanced or metastatic non-squamous NSCLC with sensitizing EGFR mutations positive (either Exon 19 deletion or 21 L858R, confirmed by histology or cytology ), and classified as stage IIIB, IIIC, IV or recurrent NSCLC which are not amenable to curative surgery or radiotherapy;
- Life expectancy of at least 3 months at recruitment;
- Only the patients receiving osimertinib as 1L treatment and meeting the following criteria will be considered:
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- Prior to 1L osimertinib:
- History of EGFRm (exon 19 deletion or exon 21 L858R) in the plasma ctDNA by the local testing methods.
- No previous systemic treatment. Adjuvant therapies, or definitive radiation/chemoradiation are permitted as long as treatment was completed at least 6 months prior to receiving 1L treatment.
- Patients with asymptomatic and stable CNS metastases for at least 2 weeks will be allowed, including leptomeningeal metastases.
- Prior to randomization: Patients after 3 weeks of 1L osimertinib treatment who have persistence ctDNA EGFRm by SuperARMS at 3 weeks will be considered to be enrolled. They will need to further meet the criteria below before randomization:
- Patients without disease progression by RECIST 1.1 evaluation;
- At least 1 measurable extracranial lesion according to RECIST 1.1 .
- Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential.
- Male subjects should be willing to agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
Who cannot join
- Involvement in the planning and/or conduct of the study;
- History of hypersensitivity to active or inactive excipients of Osimertinib and/or Pemetrexed and/or Carboplatin or drugs with a similar chemical structure or class to Osimertinib and/or Pemetrexed and/or Carboplatin;
- For patients, inability to collect plasma samples at baseline and disease progression;
- QT prolongation or any clinically important abnormalities in rhythm;
- Any evidence of severe or uncontrolled systemic diseases;
- Currently receiving medications or herbal supplements known to be strong inducers of CYP3A4;
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- Any unresolved toxicities from prior therapy greater than CTCAE 5.0 grade 1 at the time of starting study treatment.
- 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.
- Inadequate bone marrow reserve or organ function;
- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
- Contraindication for osimertinib, pemetrexed and carboplatin according to China approved label.
- Women who are pregnant or breast-feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Efficacy and Safety of Osimertinib Plus Carboplatin and Pemetrexed Versus Osimertinib Monotherapy in Locally Advanced or Metastatic EGFRm NSCLC Patients With EGFRm Persistence in ctDNA at 3 Weeks After 1L Osimertinib: A Multicenter, Randomized Controlled Study
This is a prospective, randomised, open-label, positive-controlled study to investigate the efficacy and safety of Osimertinib plus Carboplatin/Pemetrexed versus Osimertinib monotherapy in locally advanced or metastatic EGFRm NSCLC patients with EGFRm persistence in ctDNA at 3 weeks after first-line therapy with Osimertinib.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Osimertinib, Pemetrexed/Carboplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OsimertinibDrug
Also called AZD9291, Tagrisso
Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Pemetrexed/CarboplatinDrug
Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Osimertinib 80 mg QD and platinum-based chemotherapy | Experimental | Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. Receives: Drug: Osimertinib; Drug: Pemetrexed/Carboplatin |
| Osimertinib 80mg QD | Active comparator | All patients randomized into this will only receive Osimertinib 80mg. Receives: Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Measured: The analysis of PFS based on Investigator assessment (according to RECIST 1.1) will occur when approximately 54 progression events have been observed in the 80 randomized patients (approximately 67.5% PFS maturity).
Secondary outcomes (7)
OS rate at 18 months
Proportion of patients alive at 18 months
Measured: The OS rate at 18 months will be defined as the Kaplan-Meier estimate of OS at 18 months.
Objective Response Rate (ORR)
ORR (per RECIST 1.1 using Investigator assessments) is defined as the number (percent) of patients with at least 1 visit response of CR or PR.
Measured: Objective Response Rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Disease Control Rate (DCR)
Disease control rate (DCR) is defined as the percentage of subjects who have a best overall response of CR or PR or SD by RECIST 1.1 as assessed by the Investigator.
Measured: Disease control rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Measured: Duration of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Depth of Response
Depth of response by Investigator is defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of NLs or progression of NTLs when compared to baseline.
Measured: Depth of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Safety and tolerability: Adverse event
All Adverse events/≥grade 3 AE/SAE incidence rate (AE/SAE graded by CTCAE v5); All ADR incidence rate; AESI: ILD/pneumonitis-like event, Cardiac failure
Measured: Safety and tolerability analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Molecular resistance mechanism
To evaluate potential molecular resistance mechanism by biomarker analysis of plasma at baseline and disease progression and tissue samples (if applicable) by next-generation sequencing (NGS).
Measured: Molecular resistance mechanism analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2021
- Study start7 Feb 2022
- Primary completion26 Jan 2026
- Study completion26 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing Cancer Prevention & Treatment Society
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04769388
- Sponsor's protocol ID
- ESR-19-20439
- Acronym
- FLAME
- Status last verified
- Nov 2026
- First submitted
- 19 Feb 2021
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Osimertinib Plus Carboplatin and Pemetrexed Versus Osimertinib Monotherapy in Locally Advanced or Metastatic EGFRm NSCLC Patients With EGFRm Persistence in ctDNA at 3 Weeks After 1L Osimertinib: A Multicenter, Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT04769388
- Acronym / sponsor ID
- FLAME / ESR-19-20439
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Beijing Cancer Prevention & Treatment SocietyUniversity, hospital or other
- Collaborators
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Study start
- 7 Feb 2022 (actual)
- Primary completion
- 26 Jan 2026 (actual)
- Study completion
- 26 Jan 2026 (actual)
- First posted
- 24 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, randomised, open-label, positive-controlled study to investigate the efficacy and safety of Osimertinib plus Carboplatin/Pemetrexed versus Osimertinib monotherapy in locally advanced or metastatic EGFRm NSCLC patients with EGFRm persistence in ctDNA at 3 weeks after first-line therapy with Osimertinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Osimertinib 80 mg QD and platinum-based chemotherapy | Experimental | Drug: Osimertinib, Drug: Pemetrexed/CarboplatinOsimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. |
| Osimertinib 80mg QD | Active comparator | Drug: OsimertinibAll patients randomized into this will only receive Osimertinib 80mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Provision and signed of informed consent prior to any study specific procedures;
- Male or female, aged at least 18 years;
- Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1;
- Newly diagnosed, and histologically documented locally advanced or metastatic non-squamous NSCLC with sensitizing EGFR mutations positive (either Exon 19 deletion or 21 L858R, confirmed by histology or cytology ), and classified as stage IIIB, IIIC, IV or recurrent NSCLC which are not amenable to curative surgery or radiotherapy;
- Life expectancy of at least 3 months at recruitment;
Key exclusion criteria (13 listed)
- Involvement in the planning and/or conduct of the study;
- History of hypersensitivity to active or inactive excipients of Osimertinib and/or Pemetrexed and/or Carboplatin or drugs with a similar chemical structure or class to Osimertinib and/or Pemetrexed and/or Carboplatin;
- For patients, inability to collect plasma samples at baseline and disease progression;
- QT prolongation or any clinically important abnormalities in rhythm;
- Any evidence of severe or uncontrolled systemic diseases;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OsimertinibAlso: AZD9291, TagrissoPemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. | Drug | Osimertinib 80 mg QD and platinum-based chemotherapy, Osimertinib 80mg QD |
| Pemetrexed/CarboplatinPemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. | Drug | Osimertinib 80 mg QD and platinum-based chemotherapy |
Primary outcome
Progression free survival
Time frame: The analysis of PFS based on Investigator assessment (according to RECIST 1.1) will occur when approximately 54 progression events have been observed in the 80 randomized patients (approximately 67.5% PFS maturity).
Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
7 secondary outcomes
OS rate at 18 months
Time frame: The OS rate at 18 months will be defined as the Kaplan-Meier estimate of OS at 18 months.
Objective Response Rate (ORR)
Time frame: Objective Response Rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Disease Control Rate (DCR)
Time frame: Disease control rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Duration of Response (DoR)
Time frame: Duration of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Depth of Response
Time frame: Depth of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Safety and tolerability: Adverse event
Time frame: Safety and tolerability analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Molecular resistance mechanism
Time frame: Molecular resistance mechanism analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 31 months from the first patient being randomized.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Osimertinib and Pemetrexed/Carboplatin in people with Non Small Cell Lung Cancer, run by Beijing Cancer Prevention & Treatment Society at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: The analysis of PFS based on Investigator assessment (according to RECIST 1.1) will occur when approximately 54 progression events have been observed in the 80 randomized patients (approximately 67.5% PFS maturity).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.