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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: ASP8273


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I dose-escalation group<br>Oral administration | Drug: ASP8273<br>* Oral administration<br>|
| Experimental: Phase I EGFR-T790M mutation group<br>Oral administration | Drug: ASP8273<br>* Oral administration<br>|
| Experimental: Phase II group<br>Oral administration | Drug: ASP8273<br>* Oral administration<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, pharmacokinetics, tolerability, ASP8273, Non-small Cell Lung Cancer, T790M resistance mutation, NSCLC, Epidermal Growth Factor Receptor mutations, irreversible EGFR inhibitor, antitumor activity, EGFR