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Non-small Cell Lung CancerPhase 2/3BMNCT03653546

First Line Treatment in EGFR Mutation Positive Advanced NSCLC Patients With Central Nervous System (CNS) Metastases

A Phase 2/3 study testing AZD3759, Erlotinib and Gefitinib in people with Non-small Cell Lung Cancer and EGFR Gene Mutation, run by Alpha Biopharma (Jiangsu) Co., Ltd. at 58 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The first-line treatment with single agent AZD3759 results in superior Progression Free Survival (PFS) compared to Standard of Care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI), in patients with advanced EGFR mutation positive non-small cell lung cancer (NSCLC) with Central Nervous… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AZD3759, Erlotinib and Gefitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
492 participants
Where
58 sitesin 4 countries
Study dates
29 Oct 2018to 12 Jul 2022
Phase
Phase 2/3
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

  • Properly completed patient informed consent
  • Male or female aged at least 18 years
  • Histologically or cytologically confirmed diagnosis of NSCLC with activating EGFR mutations including L858R and/or Exon19Del. EGFR mutation status will be determined by local or central laboratory testing on tumour tissue or plasma utilizing a validated methodology which has been approved by the regulatory authority.
  • No prior treatment with chemotherapy, EGFR-TKIs, or biological therapies that are considered first line treatment for advanced NSCLC.
  • All patients must have a documented diagnosis of advanced (Stage IV) NSCLC with Magnetic Resonance Imaging (MRI) documented CNS metastases that include brain metastases (BM). BM + patients with co- existent leptomeningeal involvement are eligible for the study.
  • Eligible patients are not candidates for definitive surgical resection or radiation of all lesions in the opinion of the treating physician.
Show all 11Show fewer
  • All patients must be stable without any systemic (oral or parenteral) corticosteroid or anticonvulsant therapy for at least 2 weeks prior to study treatment. Inhaled non-absorbable and topical corticosteroid use are permitted as indicated.
  • Patients may have prior placement of a properly functioning CNS shunt or Ommaya reservoir.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks.
  • Women of child-bearing potential and male subjects shall agree to take medically acceptable contraception measures while on study treatment and for 3 months following completion of study treatment. All women of child-bearing potential must have a negative blood pregnancy test at screening.
  • (a) For Patients with measurable CNS lesions must have AT LEAST ONE site of CNS lesion, which was not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter by MRI and which is suitable for accurate repeated measurements. Measurable extracranial disease is not required. (b) For Patients with non-measurable CNS lesions must have AT LEAST ONE extracranial lesion, which has not been previously irradiated, within the screening period that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) by CT/MRI and are suitable for accurate repeated measurement.

Who cannot join

None listed.

Trial locations and contacts

58 sites in 4 countries.

58 sites in 4 countries

China41 sites

  • China site

    Beijing, 100021

  • China site

    Beijing, 100071

  • China site

    Beijing, 100142

  • China site

    Beijing, 100730

  • China site

    Changchun, Jilin, 130012

  • China site

    Changchun, Jilin, 130021

  • China site

    Changsha, Hunan, 410013

  • China site

    Chengdu, Sichuan, 610041

  • China site

    Chongqing, China, 400037

  • China site

    Chongqing, 400030

  • China site

    Chongqing, 400042

  • China site

    Fuzhou, Fujian, 350014

  • China site

    Guangzhou, Guangdong, 510080

  • China site

    Guangzhou, Guangdong, 510180

  • China site

    Haerbin, Heilongjiang, 150081

  • China site

    Hangzhou, Zhejiang, 310003

  • China site

    Hangzhou, Zhejiang, 310022

  • China site

    Hangzhou, Zhejiang, 311100

  • China site

    Hefei, Anhui, 230001

  • China site 0123

    Jinan, Shandong, 250117

  • China site

    Kunming, Yunnan, 650118

  • China site

    Linyi, Shandong, 276000

  • China site

    Nanjing, Jiangsu, 210002

  • China site

    Nanjing, Jiangsu, 210009

  • China site

    Shanghai, 200030

  • China site

    Shanghai, 200032

  • China site

    Suzhou, Jiangsu, 215004

  • China site

    Tianjin, 300052

  • China site

    Weifang, Shandong, 261000

  • China site

    Wuhan, Hubei, 430022

  • China site

    Wuhan, Hubei, 430030

  • China site

    Wuhan, Hubei, 430079

  • China site

    Wuxi, Jiangsu, 214062

  • China site

    Xi'an, Shaanxi, 710061

  • China site

    Xiamen, Fujian, 361003

  • China site

    Xuzhou, Jiangsu, 221002

  • China site

    Yangzhou, Jiangsu, 225001

  • China site

    Yantai, Shandong, 264000

  • China site

    Yichang, Hubei, 443003

  • China site

    Zhengzhou, Henan, 450008

  • China site

    Zhengzhou, Henan, 450052

Other trials in China

South Korea12 sites

  • Korea site

    Daegu, 42415

  • Korea site

    Gyeonggi-do, 16247

  • Korea site

    Gyeongsang, 52727

  • Korea site

    Incheon, 21565

  • Korea Site

    Jungbuk, 28644

  • Korea Site

    Seoul, 03080

  • Korea site

    Seoul, 05368

  • Korea Site

    Seoul, 06351

  • Korea site

    Seoul, 06591

  • Korea site

    Seoul, 07061

  • Korea site

    Suwon, 16499

  • Korea site

    Ulsan, 44033

Other trials in South Korea

Taiwan4 sites

  • Taiwan site

    Taichung, 407

  • Taiwan site

    Tainan, 704

  • Taiwan site

    Taipei, 100

  • Taiwan site

    Taoyuan, 333

Other trials in Taiwan

Singapore1 site

  • Singapore site

    Singapore, 308433

Other trials in Singapore

About this study

Official title: A Randomized, Open-label, Controlled, Multi-Center Phase II/III Study to Assess the Efficacy and Safety of AZD3759 vs. a Standard of Care EGFR TKI, as First Line Treatment to EGFR Mutation Positive Advanced NSCLC With CNS Metastases

The first-line treatment with single agent AZD3759 results in superior Progression Free Survival (PFS) compared to Standard of Care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI), in patients with advanced EGFR mutation positive non-small cell lung cancer (NSCLC) with Central Nervous System (CNS) metastasis

Read the detailed description

This is a Phase II/III randomized, open-label, multicenter study to compare the efficacy and safety of first line single-agent AZD3759 vs. Erlotinib or Gefitinib treatment in patients with advanced EGFR mutation positive NSCLC with CNS metastases.

Eligible patients with documented EGFR mutation+ (L858R and/or Exon 19Del) TKI-naïve advanced NSCLC and documented intracranial disease will be enrolled.

Being tested
AZD3759, Erlotinib, Gefitinib
Keywords
Central Nervous System Metastases, Respiratory Tract Diseases, EGFR, Exon 19Del, L858R, Lung Neoplasm, Carcinoma, Non-Small-Cell Lung, Neoplasms
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Respiratory Tract Diseases, Lung Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD3759Drug

    AZD3759 200mg PO BID.

  • ErlotinibDrug

    Also called Tarceva

    SoC EGFRTKI Erlotinib 150 mg PO Q.D

  • GefitinibDrug

    Also called Iressa

    SoC EGFRTKI Gefitinib 250 mg PO Q.D

Study groups in NCT03653546
Study groupRoleWhat they receive
AZD3759 GroupExperimentalAZD3759 group will receive a 200 mg twice daily dose of AZD3759
Receives: Drug: AZD3759
Erlotinib or Gefitinib GroupActive comparatorSoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D
Receives: Drug: Erlotinib; Drug: Gefitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PFS assessed by Blinded Independent Central Radiological

    To assess if first line treatment with AZD3759 results in significant PFS efficacy compared to Gefitinib or Erlotinib as determined by Blinded Independent Central Radiological (BICR) review using RECIST 1.1.

    Measured: 48 months

Secondary outcomes (29)

  1. PFS assess by investigator

    Investigator assessment of PFS using RECIST 1.1

    Measured: 48 months

  2. Intracranial PFS (iPFS) assessed by investigator

    Intracranial PFS (iPFS) assessed by investigator using RECIST 1.1

    Measured: 48 months

  3. Intracranial PFS (iPFS) assessed by BICR

    Intracranial PFS (iPFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1

    Measured: 48 months

  4. Extracranial PFS (ePFS) assessed by investigator

    Extracranial PFS (ePFS) assessed by investigator using RECIST 1.1

    Measured: 48 months

  5. Extracranial PFS (ePFS) assessed by BICR

    Extracranial PFS (ePFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1

    Measured: 48 months

  6. Objective Response Rate (ORR） assessed by investigator using RECIST 1.1

    Objective Response Rate (ORR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1

    Measured: 48 months

  7. Disease Control Rate (DCR) assessed by investigator using RECIST 1.1

    Disease Control Rate (DCR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1

    Measured: 48 months

  8. Duration of Response (DoR) assessed by investigator using RECIST 1.1

    Duration of Response (DoR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1

    Measured: 48 months

  9. Overall ORR assessed by investigator using RECIST 1.1

    Overall ORR assessed by investigator using RECIST 1.1

    Measured: 48 months

  10. Overall DCR assessed by investigator using RECIST 1.1

    Overall DCR assessed by investigator using RECIST 1.1

    Measured: 48 months

  11. Overall DoR assessed by investigator using RECIST 1.1

    Overall DoR assessed by investigator using RECIST 1.1

    Measured: 48 months

  12. ORR for Intracranial lesions assessed by investigator using RANO-BM

    ORR for Intracranial lesions assessed by investigator using RANO-BM

    Measured: 48 months

  13. DCR for Intracranial lesions assessed by investigator using RANO-BM

    DCR for Intracranial lesions assessed by investigator using RANO-BM

    Measured: 48 months

  14. DoR for Intracranial lesions assessed by investigator using RANO-BM

    DoR for Intracranial lesions assessed by investigator using RANO-BM

    Measured: 48 months

  15. Overall Survival

    Overall Survival

    Measured: 48 months

  16. Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).

    The 30-items questionnaire measures cancer patients' functioning and symptoms. The scale range of EORTC QLQ-C30 is 30-126. Lower values represent a better outcome.

    Measured: 48 months

  17. Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire BN20 (EORTC QLQ-BN20).

    The 20-items questionnaire was used among brain cancer patients. The scale range of EORTC BN20 is 20-80. Lower values represent a better outcome.

    Measured: 48 months

  18. Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE)

    Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE)

    Measured: 48 months

  19. Neurological function improvement rate assessed by RANO-BM criteria

    Neurological function improvement rate assessed by RANO-BM criteria

    Measured: 48 months

  20. Number of participants with treatment-related Adverse Events as assessed by CTCAE v5.0

    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: 48 months

  21. Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0

    Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0

    Measured: 48 months

  22. Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0

    Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0

    Measured: 48 months

  23. Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0

    Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0

    Measured: 48 months

  24. Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0

    Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0

    Measured: 48 months

  25. Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period.

    Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period.

    Measured: 48 months

  26. Systolic and Diastolic Blood Pressure assessed during the study period.

    Systolic and Diastolic Blood Pressure assessed during the study period.

    Measured: 48 months

  27. Pulse rate assessed during the study period.

    Pulse rate to assessed during the study period.

    Measured: 48 months

  28. Body temperature assessed during the study period.

    Body temperature assessed during the study period.

    Measured: 48 months

  29. PFS assess by BICR

    Blinded Independent Central Radiological (BICR) assessment of PFS using modified RECIST 1.1.

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study start29 Oct 2018
  3. Primary completion12 Jul 2022
  4. Study completion12 Jul 2022

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
492 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03653546
Sponsor's protocol ID
AZD3759-003
Acronym
BM
Status last verified
Sep 2025
First submitted
22 Aug 2018
Last updated
10 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhou Q, Yu Y, Xing L, Cheng Y, Wang Y, Pan Y, Fan Y, Shi J, Zhang G, Cui J, Zhou J, Song Y, Zhuang W, Ma Z, Hu Y, Li G, Dong X, Feng J, Lu S, Wu J, Li J, Zhang L, Wang D, Xu X, Yang TY, Yang N, Guo Y, Zhao J, Yao Y, Zhong D, Xia B, Yang CT, Zhu B, Sun P, Shim BY, Chen Y, Wang Z, Ahn MJ, Wang J, Wu YL. First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial. Med. 2025 Jan 10;6(1):100513. doi: 10.1016/j.medj.2024.09.002. Epub 2024 Oct 9.

    PubMed 39389055

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing AZD3759, Erlotinib and Gefitinib in people with Non-small Cell Lung Cancer and EGFR Gene Mutation, run by Alpha Biopharma (Jiangsu) Co., Ltd. at 58 sites in 4 countries.

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 11 inclusion and 0 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 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in China, South Korea, Taiwan, Singapore. 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

PFS assessed by Blinded Independent Central Radiological (time frame: 48 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03653546, which also lists 1 linked publication.

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 10 Sep 2025.

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