ASK120067 Versus Gefitinib as First-line Treatment for EGFRm Locally Advanced or Metastatic NSCLC

NCT04143607 | Active Not Recruiting Phase 3

• 1 other identifier: ASK-LC-120067-F-III
• Study Type: interventional
• Target: 337
• Locations: 1 country
• Sites: 3

Brief Summary

To assess the efficacy and safety of ASK120067 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor Gefitinib in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

Conditions

Locally Advanced or Metastatic NSCLC

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS)

  Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy prior to progression and was used to assess the efficacy of single agent ASK120067 compared with Gefitinib as measured by PFS.

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

Secondary Outcomes (5)

• Objective Response Rate (ORR)

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

• Duration of Response (DoR)

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

• Disease Control Rate (DCR)

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

• Depth of Response

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

• Overall Survival (OS)- Number of Participants With an Event

  Time from treatment start to the time of death due to any cause or withdrawal from study,whichever came first, assessed up to approximately 5 years

Other Outcomes (1)

• intracranial Progression-free survival (iPFS), intracranial Objective Response rate (iORR), intracranial duration of response (iDOR), intracranial Disease Control Rate (iDCR), and intracranial Depth of Response (iDepOR)

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

Study Arms (2)

ASK120067+ placebo Gefitinib

EXPERIMENTAL

ASK120067 (80 mg orally, twice daily) plus placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule.

Drug: ASK120067; Drug: Placebo Gefitinib 250 mg

Gefitinib + placebo ASK120067

ACTIVE COMPARATOR

Gefitinib (250 mg orally, once daily) plus placebo ASK120067 (80 mg orally, twice daily), in accordance with the randomization schedule.

Drug: Gefitinib; Drug: Placebo ASK120067

Interventions

ASK120067 DRUG

ASK120067 (80 mg orally twice daily) . A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit according to RECIST 1.1, as judged by the Investigator, and in the absence of discontinuation criteria.

ASK120067+ placebo Gefitinib

Placebo Gefitinib 250 mg DRUG

The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit according to RECIST 1.1, as judged by the Investigator, and in the absence of discontinuation criteria.

Also known as: Placebo Iressa 250 mg

ASK120067+ placebo Gefitinib

Gefitinib DRUG

Gefitinib (250 mg orally, once daily) , A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit acording to RECIST 1.1, as judged by the Investigator, and in the absence of discontinuation criteria.

Gefitinib + placebo ASK120067

Placebo ASK120067 DRUG

Placebo ASK120067orally 80mg twice daily . A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit according to RECIST 1.1, as judged by the Investigator, and in the absence of discontinuation criteria.

Gefitinib + placebo ASK120067

Eligibility Criteria

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

You may qualify if:

• Male or female, aged at least 18 years.
• Histopathologically or pathologically confirmed adenocarcinoma of the lung.
• Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy(including those with newly diagnosed or postoperative recurrent stage IIIb, IIIc, or IV cancer).
• The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R) that have been confirmed by the central laboratory testing report before enrollment (through tissue samples for testing cannot be derived from tumor lesions that have undergone radiotherapy, but can be obtained from newly developed lesions after local treatment) .
• Patients must be treatment-naïve for locally advanced or metastatic NSCLC (excluding local treatment for non-target lesions) and eligible to receive first-line treatment. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents) if there is no disease progression one year after completion of treatment. Patients who have received local treatment (such as radiotherapy or pleural perfusion therapy) can participate in the study if the lesions covered by local treatment are non-target lesions.
• At baseline, at least one tumor lesion must meet the following criteria:
• (i) It has not been previously treated with radiotherapy and has not been used for biopsy during the screening period; (ii) It can be accurately measured, with the longest diameter of ≥10 mm at baseline (lymph nodes must have a short axis of ≥15 mm); (iii) It can be assessed using both CT and MRI scans, but the same testing method must be used for subsequent evaluations.
• Expected survival ≥ 3 months.
• ECOG score of 0 to 1.
• Reproductive-aged women must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result must be negative.
• Reproductive-aged women should use strict contraceptive measures throughout the entire trial period and for 3 months after the last administration of the investigational drug. Male subjects should use strict contraceptive measures and should not engage in sperm donation throughout the entire trial period and for 6 months after the last administration of the investigational drug.
• Provision of informed consent prior to any study specific procedures, sampling, and analysis.

You may not qualify if:

• Treatment with any of the following:
• Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC;
• Prior treatment with an EGFR-TKI;
• Major surgery within 4 weeks of the first dose of study drug;
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug;
• Patients currently (within 7 days before the first administration) receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4;
• Patients who have received pleural infusion therapy must have stable pleural effusion for 28 days or more before they can be enrolled (intrapleural infusion therapy may use cytokines and immunostimulants, but not biological products or other drugs with long half-lives);
• Local radiotherapy or palliative radiotherapy for bone metastases within 14 days before the first administration of the investigational drug;
• Patients are receiving treatment with drugs that are known to prolong the QTc interval or potentially cause torsade de pointes, and require continued treatment with these drugs during the study;
• Discontinuation of other clinical trial drugs for less than 14 days prior to the first administration.
• Patients with spinal cord compression or brain/meningeal metastases (except those who are asymptomatic, in stable condition, and do not require treatment with steroids for at least 4 weeks before the start of study treatment; patients who have received local radiotherapy for brain metastases must have remained stable for at least 28 days after radiotherapy before enrollment);
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of ASK120067.
• Any of the following cardiac criteria:
• The average corrected (using the Fridericia formula) QT interval (QTcF), obtained from three resting electrocardiogram (ECG) examinations, is greater than 450 ms for males or 470 ms for females;

Sponsors & Collaborators

• Jiangsu Aosaikang Pharmaceutical Co., Ltd.: lead

Study Sites (3)

Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Beijing Chest Hospital,Capital Medical University

Beijing, Beijing Municipality, 101149, China

Location

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

Location

Related Publications (1)

• Shi Y, Wu L, Ji Y, Chen G, Li B, Bi M, Yang R, Miao L, Zhang G, Gao H, Sun L, Zhang M, Cang S, Sun M, Yao W, Pan Z, Cui J, Xiao Y, Wang Q; NCT04143607 Study Group. Efficacy and safety of limertinib versus gefitinib as first-line treatment for locally advanced or metastatic non-small-cell lung cancer with EGFR-sensitising mutation: a randomised, double-blind, double-dummy, phase 3 trial. Lancet Respir Med. 2025 Aug;13(8):677-686. doi: 10.1016/S2213-2600(25)00121-3. Epub 2025 Jun 20.

  PMID: 40550238 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Triple (Participant, Investigator, Outcomes Assessor)

Study Record Dates

• First Submitted: October 12, 2019
• First Posted: October 29, 2019
• Study Start: July 23, 2019
• Primary Completion: March 31, 2024
• Study Completion (Estimated): September 30, 2026
• Last Updated: June 14, 2024

Record last verified: 2024-06

Locations

CN (3)