An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations

An Open-label Study of the Oral Administration of ASP8273 in Patients With Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor (EGFR) Mutations

Purpose of the study is to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

• the safety and tolerability of ASP8273.
• the pharmacokinetics (PK) of ASP8273.
• the antitumor activity of ASP8273.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: ASP8273

Detailed Description

This study consists of Phase I and Phase II.

The objectives of Phase I are to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

• safety and tolerability of ASP8273.
• the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of ASP8273 based on the dose limiting toxicity (DLT) profile.
• pharmacokinetics (PK) of ASP8273.
• antitumor activity of ASP8273.

The objectives of Phase II are to determine the following at the RP2D of ASP8273 in patients with NSCLC harboring EGFR mutation.

• efficacy of ASP8273
• safety of ASP8273
• PK of ASP8273

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Site: 4
  • Fukuoka, Japan
    • Site: 9
  • Miyagi, Japan
    • Site: 8
  • Okayama, Japan
    • Site: 7
  • Osaka, Japan
    • Site: 3
  • Osaka, Japan
    • Site: 6
  • Shizuoka, Japan
    • Site: 2
  • Tokyo, Japan
    • Site: 1
  • Tokyo, Japan
    • Site: 5
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Site: 10
  • Seoul, Korea, Republic of
    • Site: 11
  • Seoul, Korea, Republic of
    • Site: 12
• Taiwan
  • Taipei, Taiwan
    • Site: 13
  • Taipei, Taiwan
    • Site: 14

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of NSCLC.
• Patients confirmed to have the del ex19, L858R, G719X, or L861Q mutation among the EGFR activating mutations (patients at the study site who are documented to have any of the above-stated EGFR activating mutations can be enrolled in the study).
• Life expectancy ≥ 12 weeks based on the investigator's/subinvestigator's judgment.

• [Phase I]

  • Patients who have previously been treated with EGFR tyrosine-kinase inhibitors (EGFR-TKIs)*
  • Those who are not expected to show a therapeutic response to existing treatments in the investigator's/subinvestigator's opinion.

• [Phase II]

  • Patients who have been confirmed to have progressive disease (PD) after previous treatment with EGFR-TKIs*; for those who have received 2 or more regimens of previous treatment, the last regimen before enrollment should have included EGFR-TKIs.
  • *Erlotinib, gefitinib, and EGFR-TKIs under clinical investigation (e.g., neratinib, afatinib, dacomitinib)
  • Expression of the EGFR-T790M mutation as confirmed by a tumor biopsy of the primary or metastatic lesions after confirmation of PD following previous treatment with EGFR-TKIs and before enrollment, or by a tumor tissue sample that had been collected and archived after confirmation of PD following previous treatment with EGFR-TKIs.
  • At least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Exclusion Criteria:

• Persistent clinical evidence of previous antitumor treatment related toxicity ≥ Grade 2 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCI CTCAE v4.0 - JCOG) (except alopecia and skin toxicities considered irrelevant in study enrollment by the investigator/sub-investigator).
• History of or concurrent interstitial lung disease
• Received treatment with a reversible EGFR-TKI (erlotinib or gefitinib) within 8 days before the start of the study treatment.
• Received previous treatment (except reversible EGFR-TKIs) intended to have antitumor effects or treatment with another investigational drug or an investigational device within 14 days before the start of the study treatment.
• Previously received treatment with EGFR-TKIs (e.g., CO-1686, AZD9291) that can inhibit EGFR with the T790M mutation.
• It is planned that the subject will undergo a surgical procedure during the course of the study or the subject still has an unhealed wound after previous surgery
• Symptomatic central nervous system (CNS) lesions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I dose-escalation group; Oral administration	Drug: ASP8273; Oral administration
Experimental: Phase I EGFR-T790M mutation group; Oral administration	Drug: ASP8273; Oral administration
Experimental: Phase II group; Oral administration	Drug: ASP8273; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Safety and tolerability of ASP8273 as assessed by Dose Limiting Toxicities (DLTs)	A DLT is defined as any pre-determined toxicity that is related to study drug per the investigator and which occurs during Cycle 0 and Cycle 1 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE ver 4.0 - JCOG)	Up to Day 23
Phase II: Overall response rate (CR+PR) at Week 24	The overall response rate, which is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Safety and tolerability of ASP8273 as assessed by adverse events (AEs)	An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product	Up to 18 months
Phase I: Safety and tolerability of ASP8273 as assessed by laboratory tests	Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation	Up to 18 months
Phase I: Safety and tolerability of ASP8273 as assessed by vital signs	Vital signs to be measured includes blood pressure, pulse rate and temperature	Up to 18 months
Phase I: Safety and tolerability of ASP8273 as assessed by 12-lead ECG	including the assessment of QT intervals	Up to 18 months
Phase I: Plasma concentrations of unchanged ASP8273		Up to Day 1 of Cycle 3
Phase I: Urine concentrations of unchanged ASP8273		Up to Day 1 of Cycle 3
Phase I: Overall response rate (CR+PR)	The overall response rate is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated	Up to 18 months
Phase I: Disease control rate (CR+PR+SD)	The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.	Up to 18 months
Phase II: Plasma concentrations of unchanged ASP8273		Up to Day 1 of Cycle 3
Phase II: Urine concentrations of unchanged ASP8273		Up to Day 1 of Cycle 3
Phase II: Safety and tolerability of ASP8273 as assessed by adverse events (AEs)	An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product	Up to 18 months
Phase II: Safety and tolerability of ASP8273 as assessed by laboratory tests	Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation	Up to 18 months
Phase II: Safety and tolerability of ASP8273 as assessed by vital signs	Vital signs to be measured includes blood pressure, pulse rate and temperature	Up to 18 months
Phase II: Safety and tolerability of ASP8273 as assessed by 12-lead ECG	including the assessment of QT intervals	Up to 18 months
Phase II: Disease control rate	The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.	Up to 18 months
Phase II: Progression-free survival (PFS)		Up to 18 months
Phase II: Overall survival (OS)		Up to 18 months
Phase II: Overall response rate (CR+PR)	The overall response rate, which is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated	Up to 18 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Medical Director, Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2014
• Primary Completion (Actual): January 15, 2016
• Study Completion (Actual): June 14, 2017

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: July 15, 2014
• First Posted (Estimated): July 17, 2014

Study Record Updates

• Last Update Posted (Actual): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: tolerability; safety; NSCLC; pharmacokinetics; EGFR; Non-small Cell Lung Cancer; ASP8273; T790M resistance mutation; irreversible EGFR inhibitor; Epidermal Growth Factor Receptor mutations; antitumor activity
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Naquotinib
• Other Study ID Numbers: 8273-CL-0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR