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NSCLCPhase 1NCT02973763

Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Alflutinib in Advanced Non Small Cell Lung Cancer

A Phase 1 study testing Alflutinib in people with NSCLC, run by Allist Pharmaceuticals, Inc..

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Alflutinib Mesylate Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation tumor cell in Xenograft mouse model. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
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
14 participants
Where
No sites listed yet
Study dates
30 Dec 2016to 1 Aug 2023
Phase
Phase 1
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients of either gender, aged from 18 years older to 65.
  • 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.
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  • 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).
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  • 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.
  • 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.

About this study

Official title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Alflutinib in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent

Alflutinib Mesylate Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation tumor cell in Xenograft mouse model. This study aims at local advanced or metastatic non-small cell lung cancer patients with T790M drug-resistant mutation.

Read the detailed description

This is a Phase I study, to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of AST2818 in patients with advanced non-small cell lung cancer who progressed on prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor agent. The tolerability of AST2818 20 mg/day - 240 mg/day in 14 subjects was observed. 7-days observation period for a single dose and 21-days observation period for multiple doses.

Conditions
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

Study groups in NCT02973763
Study groupRoleWhat they receive
AlflutinibExperimentalpatients 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.

  1. 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

Secondary outcomes (20)

  1. Maximum Plasma Concentration [Cmax] of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out Cmax.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  2. Peak Plasma Time [tmax] of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out tmax.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  3. Area under the plasma concentration versus time curve (AUC) of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day1 to figure out AUC.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  4. Terminal rate constant of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out terminal rate constant.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  5. Clearance of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out clearance.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  6. Half life of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out half life.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  7. Volume of distribution of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out volume of distribution.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  8. Mean resistance time of single dose Alflutinib and 2 metabolites

    Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out mean resistance time.

    Measured: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)

  9. Steady state 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)

  10. Steady state 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)

  11. 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)

  12. Steady state 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)

  13. 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)

  14. 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)

  15. Time dependency of multiple doses Alflutinib and 2 metabolites

    Time dependency 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)

  16. 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, expected average 6 months

  17. 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, expected average 6 months

  18. 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, expected average 6 months

  19. Disease progression rate of Alflutinib

    Progression of tumor was assessed by RECIST 1.1 thereby to evaluate disease progression rate

    Measured: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months

  20. 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, expected average 6 months

Timeline

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

  1. First posted25 Nov 2016 (estimated)
  2. Study start30 Dec 2016
  3. Primary completion4 Feb 2021
  4. Study completion1 Aug 2023

Why it stopped: Indications have been approved for marketing

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02973763
Sponsor's protocol ID
20161121
Status last verified
Jan 2020
First submitted
21 Nov 2016
Last updated
3 Apr 2025
Results posted
No
Data monitoring committee
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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alflutinib in people with NSCLC, run by Allist Pharmaceuticals, Inc..

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 14 inclusion and 11 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.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 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?

Incidence and Severity of Treatment-Emergent Adverse Events (time frame: Adverse events will be collected from baseline until 28 days after the last dose). 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 NCT02973763, 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.

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