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
Overview
- Phase
- Phase 1
- Intervention
- ASP8273
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Astellas Pharma Inc
- Enrollment
- 124
- Locations
- 14
- Primary Endpoint
- Phase II: Overall response rate (CR+PR) at Week 24
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
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
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
Investigators
Eligibility Criteria
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.
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.
Arms & Interventions
Phase I dose-escalation group
Oral administration
Intervention: ASP8273
Phase I EGFR-T790M mutation group
Oral administration
Intervention: ASP8273
Phase II group
Oral administration
Intervention: ASP8273
Outcomes
Primary Outcomes
Phase II: Overall response rate (CR+PR) at Week 24
Time Frame: 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
Phase I: Safety and tolerability of ASP8273 as assessed by Dose Limiting Toxicities (DLTs)
Time Frame: Up to Day 23
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)
Secondary Outcomes
- Phase I: Safety and tolerability of ASP8273 as assessed by laboratory tests(Up to 18 months)
- Phase I: Disease control rate (CR+PR+SD)(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)(Up to 18 months)
- Phase II: Urine concentrations of unchanged ASP8273(Up to Day 1 of Cycle 3)
- Phase II: Safety and tolerability of ASP8273 as assessed by 12-lead ECG(Up to 18 months)
- Phase II: Progression-free survival (PFS)(Up to 18 months)
- Phase II: Safety and tolerability of ASP8273 as assessed by laboratory tests(Up to 18 months)
- Phase I: Safety and tolerability of ASP8273 as assessed by adverse events (AEs)(Up to 18 months)
- Phase I: Safety and tolerability of ASP8273 as assessed by vital signs(Up to 18 months)
- Phase I: Safety and tolerability of ASP8273 as assessed by 12-lead ECG(Up to 18 months)
- Phase II: Plasma concentrations of unchanged ASP8273(Up to Day 1 of Cycle 3)
- Phase II: Safety and tolerability of ASP8273 as assessed by vital signs(Up to 18 months)
- Phase II: Overall survival (OS)(Up to 18 months)
- Phase II: Safety and tolerability of ASP8273 as assessed by adverse events (AEs)(Up to 18 months)
- Phase II: Overall response rate (CR+PR)(Up to 18 months)
- Phase II: Disease control rate(Up to 18 months)