Advanced NSCLCNCT03127449
AST2818 in Advanced Non-Small Cell Lung Cancer With EGFR Mutations
A study testing Alflutinib in people with Advanced NSCLC, run by Allist Pharmaceuticals, Inc. at 1 site in China.
Trial summary
This study is conducted to assess the safety, tolerability and preliminary efficacy of AST2818 in patients with advanced Non Small Cell Lung Cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced NSCLC
- What is being tested?
- Alflutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2017to 8 Jan 2024
- Phase
- Interventional
- 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
- Patients of either gender, aged older than 18 years.
- Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC.
- Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib or Afatinib, or Icotinib (Third EGFR TKI are not included). In addition other lines of therapy may have been given.
- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation)
- Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy).
- ECOG performance status of 0 to 2. Life expectancy of at least 12 weeks.
Show all 9Show fewer
- At least one measurable disease by CT or PET-CT or MRI, according to RECIST Version 1.1.
- Organ function must meet the following requirements：Absolute neutrophil count >= 1.5 x 109/L, Platelet count >= 75 x 109/L, Haemoglobin >= 90 g/L；Alanine aminotransferase/Aspartate aminotransferase <= 2.5 times the upper limit of normal if no demonstrable liver metastases or <= 5 times in the presence of liver metastases；Total bilirubin <= 1.5 times ULN if no liver metastases or <= 3 times ULN in the presence of liver metastases or liver metastases；Creatinine <=1.5 times ULN concurrent with creatinine clearance >= 50 ml/min (measured or calculated by Cockcroft and Gault equation); Females should not be in lactation period and must have a negative pregnancy test prior to start of dosing; During the whole treatment,all patients should be in the entire 3 months during and after the treatment, repeated barrier precautions
- Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation.
Who cannot join
- Any cytotoxic chemotherapy from a previous treatment regimen or clinical study within 21 days，Any Target cancer drug from a previous treatment regimen or clinical study within 14 days, or less than approximately 5x half-life of the first dose of study treatment；The third EGFR-TKI from a previous treatment regimen or clinical study (ie, AZD9291, CO-1686, HM61713, ASP8273, EGF816, avitinib,
- Taking (or cannot stop taking 1 week before the first dose receiving) strong inhibitor of CYP3A4 or antitumor herb.
- Unrecovered toxic reaction due to former therapy existed, with over 1 grade of CTCAE (except alopecia) or 2 grade if ever applied DDP curing related neuropathy.
- Spinal compression, or brain metastasis exhibiting symptoms but untreated (except those exhibit no symptom with stable condition and do not apply corticosteroids for 4 weeks before the trail initiating)
- Any evidence showing severe or inadequate controlled systemic disease. For example patients with inadequate controlled hypertension considered not suitable for the trail or would affect the compliance towards the protocol, with active hemorrhagic tendency, with active infection such as HBV (HBV-DNA≥1000cps/ml), with HCV, with HIV et al (except for HBV carrier those the researcher considered meet the criterion).
- Any condition affecting the drug taking, or significantly affecting the absorption or the pharmacokinetic parameters, include any kind of uncontrollable nausea or vomit, chronic gastroenteropathy, disability in swallowing, and history of gastrointestinal resection or surgery.
Show all 10Show fewer
- Any condition meet the following cardiac standard: ECG show a QTc>470 msec under resting state (Repeat in 48 hours when a first abnormal discovered, take mean of the two measurements). All kinds of abnormal in cardiac rhythm, conduction and resting ECG profile with clinical significance, for example complete left bundle branch block, 2 or 3 grade of conduction block and a PR interval>250 msec. Any possible factors increasing the risk of QTc extending or leading to arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, any first degree relative suffered from long QT syndrome or undertook unexplained sudden death before 40 years old, or taking any drug leading to a longer QTc.
- Any history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonia require steroid therapy or active interstitial lung disease with clinical evidence during recruiting.
- Patients with other factors the researchers considered not suitable for the trail (for example, patients those who not willing to follow the procedure, limitation or requirements, who once experienced bone marrow allotransplantation, who have other kinds of malignant tumor coexisted or who showed allergic to the active ingredients or inactive adjuvant of the investigational drug, as well as drugs with similar chemical structure or in the same class).
- Confirmed mutation of EGFR 20 exon insertion at anytime after the first diagnosis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multiple-Centered Study of AST2818 in Patients With Advanced Non-small Cell Lung Cancer With EGFR Mutations
This study is conducted to assess the safety, tolerability and preliminary efficacy of AST2818 in patients with advanced Non Small Cell Lung Cancer (NSCLC).
- Conditions
- Advanced NSCLC
- Being tested
- Alflutinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlflutinibDrug
Also called AST2818
patients take Alflutinib orally once per day at different dose
| Study group | Role | What they receive |
|---|---|---|
| Alflutinib | Experimental | patients take Alflutinib orally once per day at different dose Receives: Drug: Alflutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate of Alflutinib
Evaluation of objective response rate assessed by RECIST 1.1
Measured: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Secondary outcomes (11)
Duration of response of Alflutinib
Duration of response assessed by RECIST 1.1
Measured: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Progression free survival of Alflutinib
Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival
Measured: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Clinical benefit rate of Alflutinib
Clinical benefit rate was calculated by adding up complete remission, partial remission and stabilization of disease assessed by RECIST 1.1
Measured: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Disease control rate of Alflutinib
Progression of tumor was assessed by RECIST 1.1 thereby to evaluate disease control rate
Measured: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Incidence and Severity of Treatment-Emergent Adverse Events
Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations, RECIST1.1, and NCI CTCAE v4.03
Measured: Adverse events will be collected from baseline until 28 days after the last dose
Steady state Maximum Plasma Concentration [Cmax] of multiple doses Alflutinib and 2 metabolites
Cmax of Alflutinib and 2 metabolites at steady state following multiple doses
Measured: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state peak plasma time [tmax] of multiple doses Alflutinib and 2 metabolites
tmax of Alflutinib and 2 metabolites at steady state following multiple doses.
Measured: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state Cmin (Minimum Plasma Concentration) of multiple doses Alflutinib and 2 metabolites
Cmin of Alflutinib and 2 metabolites at steady state following multiple doses.
Measured: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state area under the plasma concentration versus time curve [AUC] of multiple doses Alflutinib and 2 metabolites
AUC of Alflutinib and 2 metabolites at steady state following multiple doses.
Measured: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state clearance of multiple doses Alflutinib and 2 metabolites
Clearance of Alflutinib and 2 metabolites at steady state following multiple doses.
Measured: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Accumulation ratio of multiple doses Alflutinib and 2 metabolites
Accumulation ratio of Alflutinib and 2 metabolites following multiple doses.
Measured: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2017
- Study start1 Jun 2017
- Primary completion12 May 2021
- Study completion8 Jan 2024
Why it stopped: Indications have been approved for marketing
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced NSCLCStudies of the same condition, open and under way.
- More trials run by Allist Pharmaceuticals, Inc.The sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allist Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03127449
- Sponsor's protocol ID
- 20170405
- Status last verified
- Mar 2025
- First submitted
- 18 Apr 2017
- Last updated
- 3 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shi Y, Zhang S, Hu X, Feng J, Ma Z, Zhou J, Yang N, Wu L, Liao W, Zhong D, Han X, Wang Z, Zhang X, Qin S, Ying K, Feng J, Fang J, Liu L, Jiang Y. Safety, Clinical Activity, and Pharmacokinetics of Alflutinib (AST2818) in Patients With Advanced NSCLC With EGFR T790M Mutation. J Thorac Oncol. 2020 Jun;15(6):1015-1026. doi: 10.1016/j.jtho.2020.01.010. Epub 2020 Jan 30.
PubMed 32007598
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multiple-Centered Study of AST2818 in Patients With Advanced Non-small Cell Lung Cancer With EGFR Mutations
- ClinicalTrials.gov ID
- NCT03127449
- Acronym / sponsor ID
- 20170405
- Conditions
- Advanced NSCLC
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Indications have been approved for marketing
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Allist Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 12 May 2021 (actual)
- Study completion
- 8 Jan 2024 (actual)
- First posted
- 25 Apr 2017 (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 study is conducted to assess the safety, tolerability and preliminary efficacy of AST2818 in patients with advanced Non Small Cell Lung Cancer (NSCLC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alflutinib | Experimental | Drug: Alflutinibpatients take Alflutinib orally once per day at different dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients of either gender, aged older than 18 years.
- Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC.
- Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib or Afatinib, or Icotinib (Third EGFR TKI are not included). In addition other lines of therapy may have been given.
- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation)
- Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy).
Key exclusion criteria (10 listed)
- Any cytotoxic chemotherapy from a previous treatment regimen or clinical study within 21 days，Any Target cancer drug from a previous treatment regimen or clinical study within 14 days, or less than approximately 5x half-life of the first dose of study treatment；The third EGFR-TKI from a previous treatment regimen or clinical study (ie, AZD9291, CO-1686, HM61713, ASP8273, EGF816, avitinib,
- Taking (or cannot stop taking 1 week before the first dose receiving) strong inhibitor of CYP3A4 or antitumor herb.
- Unrecovered toxic reaction due to former therapy existed, with over 1 grade of CTCAE (except alopecia) or 2 grade if ever applied DDP curing related neuropathy.
- Spinal compression, or brain metastasis exhibiting symptoms but untreated (except those exhibit no symptom with stable condition and do not apply corticosteroids for 4 weeks before the trail initiating)
- Any evidence showing severe or inadequate controlled systemic disease. For example patients with inadequate controlled hypertension considered not suitable for the trail or would affect the compliance towards the protocol, with active hemorrhagic tendency, with active infection such as HBV (HBV-DNA≥1000cps/ml), with HCV, with HIV et al (except for HBV carrier those the researcher considered meet the criterion).
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 |
|---|---|---|
| AlflutinibAlso: AST2818patients take Alflutinib orally once per day at different dose | Drug | Alflutinib |
Primary outcome
Objective response rate of Alflutinib
Time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Evaluation of objective response rate assessed by RECIST 1.1
11 secondary outcomes
Duration of response of Alflutinib
Time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Progression free survival of Alflutinib
Time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Clinical benefit rate of Alflutinib
Time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Disease control rate of Alflutinib
Time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.
Incidence and Severity of Treatment-Emergent Adverse Events
Time frame: Adverse events will be collected from baseline until 28 days after the last dose
Steady state Maximum Plasma Concentration [Cmax] of multiple doses Alflutinib and 2 metabolites
Time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state peak plasma time [tmax] of multiple doses Alflutinib and 2 metabolites
Time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state Cmin (Minimum Plasma Concentration) of multiple doses Alflutinib and 2 metabolites
Time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state area under the plasma concentration versus time curve [AUC] of multiple doses Alflutinib and 2 metabolites
Time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Steady state clearance of multiple doses Alflutinib and 2 metabolites
Time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Accumulation ratio of multiple doses Alflutinib and 2 metabolites
Time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
Results and safety
The study was stopped early (reason given: Indications have been approved for marketing). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2025.
- Derived from this study: PubMed 32007598Shi Y, Zhang S, Hu X, Feng J, Ma Z, Zhou J, Yang N, Wu L, Liao W, Zhong D, Han X, Wang Z, Zhang X, Qin S, Ying K, Feng J, Fang J, Liu L, Jiang Y. Safety, Clinical Activity, and Pharmacokinetics of Alflutinib (AST2818) in Patients With Advanced NSCLC With EGFR T790M Mutation. J Thorac Oncol. 2020 Jun;15(6):1015-1026. doi: 10.1016/j.jtho.2020.01.010. Epub 2020 Jan 30.
- Individual participant dataSharing planned: No
Related trials for Advanced NSCLC
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
RecruitingPhase 3
Study of Daraxonrasib (RMC-6236) in Patients With RAS Mutated NSCLC (RASolve 301)
NSCLC (Non-small Cell Lung Cancer), Non-Small Cell Lung Cancer
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
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 study testing Alflutinib in people with Advanced NSCLC, run by Allist Pharmaceuticals, Inc. 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 9 inclusion and 10 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: stopped early, as of the sponsor's last update on 3 Apr 2025. 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.
Are results available for this study?
The study was stopped early (reason given: Indications have been approved for marketing). Results are not available in the source record.
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?
Objective response rate of Alflutinib (time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.). 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 NCT03127449, 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 3 Apr 2025.