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.
Name: ASP8273
Description: Oral administrationType: DrugPhase I EGFR-T790M mutation group Phase I dose-escalation group Phase II group
Description: 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)
Measure: Phase I: Safety and tolerability of ASP8273 as assessed by Dose Limiting Toxicities (DLTs) Time: Up to Day 23Description: 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
Measure: Phase II: Overall response rate (CR+PR) at Week 24 Time: Week 24Description: 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
Measure: Phase I: Safety and tolerability of ASP8273 as assessed by adverse events (AEs) Time: Up to 18 monthsDescription: Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation
Measure: Phase I: Safety and tolerability of ASP8273 as assessed by laboratory tests Time: Up to 18 monthsDescription: Vital signs to be measured includes blood pressure, pulse rate and temperature
Measure: Phase I: Safety and tolerability of ASP8273 as assessed by vital signs Time: Up to 18 monthsDescription: including the assessment of QT intervals
Measure: Phase I: Safety and tolerability of ASP8273 as assessed by 12-lead ECG Time: Up to 18 monthsDescription: 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
Measure: Phase I: Overall response rate (CR+PR) Time: Up to 18 monthsDescription: 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.
Measure: Phase I: Disease control rate (CR+PR+SD) Time: Up to 18 monthsDescription: 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
Measure: Phase II: Safety and tolerability of ASP8273 as assessed by adverse events (AEs) Time: Up to 18 monthsDescription: Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation
Measure: Phase II: Safety and tolerability of ASP8273 as assessed by laboratory tests Time: Up to 18 monthsDescription: Vital signs to be measured includes blood pressure, pulse rate and temperature
Measure: Phase II: Safety and tolerability of ASP8273 as assessed by vital signs Time: Up to 18 monthsDescription: including the assessment of QT intervals
Measure: Phase II: Safety and tolerability of ASP8273 as assessed by 12-lead ECG Time: Up to 18 monthsDescription: 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.
Measure: Phase II: Disease control rate Time: Up to 18 monthsDescription: 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
Measure: Phase II: Overall response rate (CR+PR) Time: Up to 18 monthsAllocation: Non-Randomized
Single Group Assignment
There are 3 SNPs
- 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). --- L858R ---
- 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). --- L858R --- --- L861Q ---
- *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. --- T790M ---
- Previously received treatment with EGFR-TKIs (e.g., CO-1686, AZD9291) that can inhibit EGFR with the T790M mutation. --- T790M ---