Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of ASK120067 in Locally Advanced and Metastatic Non Small Cell Lung Cancer

NCT03502850 | Unknown Phase 1

• 1 other identifier: ASK-LC-120067-Ⅰ/Ⅱ
• Study Type: interventional
• Target: 507
• Locations: 1 country
• Sites: 3

Brief Summary

ASK120067 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.

Conditions

Locally Advanced or Metastatic NSCLC

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Evaluation of objective response rate assessed by RECIST 1.1

  CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years.

Secondary Outcomes (20)

• Incidence and Severity of Treatment-Emergent Adverse Events

  Adverse events will be collected from baseline until 28 days after the last dose

• Progression free survival

  CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years.

• Duration of response

  CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years.

• Disease control rate

  CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years.

• Overall survival

  Time from treatment start to the time of death due to any cause or withdrawal from study,whichever came first, assessed up to approximately 2 years.

Study Arms (1)

ASK120067

EXPERIMENTAL

patients take ASK120067 orally once per day at different dose

Drug: ASK120067

Interventions

ASK120067 DRUG

patients take ASK120067 orally once per day at 40,80,160,240,320,480mg

ASK120067

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of either gender, aged from 18 years older to 70.
• Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC
• 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)
• 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
• 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)
• At least one lesion, not previously irradiated and not chosen for fresh biopsy during the study screening period, that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short access ≥ 15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements.
• ECOG performance status of 0 to 2.
• Life expectancy of at least 12 weeks
• 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.
• Male patients were to be willing to use barrier contraception, ie, condoms and avoid sperm donation within 6 months
• Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation

You may not qualify if:

• Any Target cancer drug from a previous treatment regimen or clinical study within 8 days, or less than approximately 5x half-life of the first dose of study treatment
• Any cytotoxic chemotherapy, investigational agents or other anticancer drugs （including traditional Chinese medicine）from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
• The third EGFR-TKI from a previous treatment regimen or clinical study (ie, AZD9291, CO-1686, HM61713, avitinib,BPI-15086,BPI-7711,Alflutinib,Almonertinib)
• Major surgery within 4 weeks of the first dose of study treatment
• Radiotherapy with a wide field of radiation or bone marrow radiotherapy is more than 30% within 4 weeks of the first dose of study treatment
• Taking (or cannot stop taking 1 week before the first dose receiving) strong inhibitor of CYP3A4
• With the exception of alopecia and grade 2 or higher, prior platinum-therapy related neuropathy, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 2 at the time of starting study treatment
• 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 or active hemorrhagic tendency considered not suitable for the trail or would affect the compliance towards the protocol
• Active infection such as HBV (HBV-DNA≥1000cps/ml), HCV, HIV, syphilis et al .
• 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: Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 ECG. 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 prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval. left ventricular ejection fraction (LVEF) within 40%.
• 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
• Hyperglycemia that cannot be stably controlled by drugs (fasting blood glucose is greater than or equal to 7.0mmol/L)
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: Absolute neutrophil count \< 1.5 x 109/L. Platelet count \< 100 x 109/L. Haemoglobin \< 90 g/L. Alanine aminotransferase\> 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases. Aspartate aminotransferase \> 2.5 times ULN if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases. Total bilirubin \> 1.5 times ULN if no liver metastases or \> 3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases Creatinine \>1.5 times ULN concurrent with creatinine clearance \< 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \> 1.5 times ULN.

Sponsors & Collaborators

• Jiangsu Aosaikang Pharmaceutical Co., Ltd.: lead

Study Sites (3)

Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

NOT YET RECRUITING

Beijing Chest Hospital,Capital Medical University

Beijing, Beijing Municipality, 101149, China

RECRUITING

Tianjin Medical University Cancer Insititute & Hospital

Tianjin, Tianjin Municipality, 300060, China

NOT YET RECRUITING

Related Publications (1)

• Shi Y, Li B, Wu L, Pan Y, Pan Z, Liu Y, Fan Y, Ji Y, Fang J, Shi Q, Shi J, Gao H, Hu Y, Wang X, He Z, Ma R, Zhang Y, Jiang D, Bai Y, Zhang Y, Huang L, Zhou T, Liu H, Wang D, Wen Q, Chen G, Zang A, Wang X, Zhang X, Hu J, Yang R, Zhang G, Gu K, Wang L, Wang Q, Wei Z, Li Z, Lu H, Zhang H, Chen H, Song T. Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter, Single-Arm, Phase 2b Study. J Thorac Oncol. 2022 Oct;17(10):1205-1215. doi: 10.1016/j.jtho.2022.05.011. Epub 2022 Jun 2.

  PMID: 35659581 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Tingting Song

CONTACT

025-85100150; songtingting@ask-pharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 19, 2018
• Study Start: November 30, 2017
• Primary Completion: January 1, 2021
• Study Completion: August 1, 2021
• Last Updated: September 16, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)