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

A Phase III,Double-Blind, Randomised Study to Assess the Efficacy and Safety of ASK120067 Versus Gefitinib as First-Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer

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

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic NSCLC
• Intervention / Treatment: Drug: ASK120067; Drug: Placebo Gefitinib 250 mg; Drug: Gefitinib; Drug: Placebo ASK120067

• Study Type: Interventional
• Enrollment (Anticipated): 334
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tingting Song; Phone Number: 025-85100150; Email: songtingting@ask-pharm.com
• Study Contact Backup: Name: Luwei Han; Phone Number: 025-85100634; Email: hanluwei@ask-pharm.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 101149
      • Recruiting
      • Beijing Chest Hospital,Capital Medical University
      • Contact: Baolan Li
      • Principal Investigator: Baolan Li
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, aged at least 18 years.
2. Pathologically confirmed adenocarcinoma of the lung.
3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents).
7. Provision of informed consent prior to any study specific procedures, sampling, and analysis.
8. ECOG score of 0 to 1

Exclusion Criteria:

1. 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 receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4.
   • Alternative anti-cancer treatment
   • Treatment with an investigational drug within five half-lives of the compound or any of its related material.
2. Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.

4、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).

5、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.

6、Any of the following cardiac criteria:Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.

7、Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.

8、Involvement in the planning and/or conduct of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASK120067+ placebo Gefitinib; ASK120067 (80 mg orally, twice daily) plus placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule.	Drug: ASK120067; 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.; Drug: Placebo Gefitinib 250 mg; 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.; Other Names: Placebo Iressa 250 mg
Active Comparator: Gefitinib + placebo ASK120067; Gefitinib (250 mg orally, once daily) plus placebo ASK120067 (80 mg orally, twice daily), in accordance with the randomization schedule.	Drug: Gefitinib; 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.; Drug: Placebo ASK120067; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the number (%) of patients with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of ASK120067 compared with Gefitinib defined as the number (%) of patients with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of ASK120067 compared with Gefitinib	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)	Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of ASK120067 compared with Gefitinib	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)	The DCR was defined as the percentage of participants who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of ASK120067 compared with Gefitinib	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	The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions	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	Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of ASK120067 compared with Gefitinib	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

Collaborators and Investigators

• Sponsor: Jiangsu Aosaikang Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Anticipated): March 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: October 12, 2019
• First Submitted That Met QC Criteria: October 28, 2019
• First Posted (Actual): October 29, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2022
• Last Update Submitted That Met QC Criteria: May 8, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: ASK-LC-120067-F-III

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No