A Phase 1b/2 Study of ASP2215 in Combination With Erlotinib in Subjects With EGFR Activating Mutation-Positive (EGFRm+) Advanced NSCLC Who Have Acquired Resistance to an EGFR Tyrosine Kinase Inhibitor (TKI)
Overview
- Phase
- Phase 1
- Intervention
- Gilteritinib
- Conditions
- Non-Small-Cell Lung Cancer
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 10
- Locations
- 4
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicities (DLTs)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
The purpose of the Phase 1b part of the study was to evaluate the safety and tolerability of ASP2215 in combination with erlotinib and determine the recommended phase 2 dose (RP2D) of ASP2215. The purpose of the Phase 2 part of the study was to evaluate the objective response rate (ORR) of the RP2D of ASP2215 in combination with erlotinib.
Detailed Description
No patients were enrolled in the Phase 2 part of the study. Phase 2 endpoints were not analyzed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant had histologically or cytologically confirmed metastatic or locally advanced, unresectable non-small-cell lung cancer (NSCLC).
- •Participant had a documented exon 19 deletion or exon 21 L858R EGFR activating mutation.
- •Participant had received prior treatment with any EGFR tyrosine kinase inhibitor
- •Participant had Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 at screening.
- •Participant had adequate organ function.
- •Female participant must either:
- •Be of nonchildbearing potential:
- •Or, if of childbearing potential,
- •Agree not to try to become pregnant during the study and for 45 days after the final study drug administration
- •And had a negative serum pregnancy test at screening
Exclusion Criteria
- •Participant had an ongoing toxicity greater than or equal to grade 3 (NCI CTCAE version 4.03) attributable to prior NSCLC treatment at the time of screening.
- •Participant received any agent with antitumor activity (other than an EGFR inhibitor, including a T790M inhibitor) including chemotherapy, radiotherapy, immunotherapy, within 14 days prior to the first dose of study drug (palliative radiotherapy is allowed).
- •Participant received ASP2215 previously.
- •Participant received blood transfusions or hematopoietic growth factor therapy within 14 days prior to the first dose of study drug.
- •Participant had a major surgical procedure (other than study-related biopsy) within 14 days prior to the first dose of study drug, or a major surgical procedure was planned to occur during the study.
- •Participant had active hepatitis B or C or other active hepatic disorder.
- •Participant t was known to have human immunodeficiency virus (HIV) infection.
- •Participant had symptomatic central nervous system (CNS) metastasis. Participants with asymptomatic, untreated CNS metastases were allowed. Participants with previously treated and currently asymptomatic CNS metastases were eligible provided they met the following:
- •Any whole brain radiotherapy (WBRT) was completed at least 2 weeks prior to the first dose of study drug.
- •Any stereotactic radiosurgery (SRS) was completed at least 1 week prior to the first dose of study drug.
Arms & Interventions
Gilteritinib 120mg + Erlotinib 150mg
Gilteritinib was administered in combination with erlotinib orally once daily.
Intervention: Gilteritinib
Gilteritinib 120mg + Erlotinib 150mg
Gilteritinib was administered in combination with erlotinib orally once daily.
Intervention: Erlotinib
Gilteritinib 80mg+ Erlotinib 150mg
Gilteritinib was administered in combination with erlotinib orally once daily.
Intervention: Gilteritinib
Gilteritinib 80mg+ Erlotinib 150mg
Gilteritinib was administered in combination with erlotinib orally once daily.
Intervention: Erlotinib
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 and Cycle ≥2 (up to 141 days)
Number of Participants With Adverse Events
Time Frame: From first dose of study drug up to 30 days after the last dose of study (maximum study drug exposure 114 days)
Treatment-emergent adverse events (TEAE) was defined as an adverse event (AE) that started after administration of the study drugs and occurred within 30 days of the last dose of the study drugs. If a participant experienced an event both during the preinvestigational period and during the investigational period, the event was considered a TEAE only if it worsened in severity.
Secondary Outcomes
- Cmax of Erlotinib(0, 0.5, 1, 2, 4, 6, 24 hours post-dose on Day 28 of cycle 1)
- Area Under the Concentration-time Curve at 24 Hours (AUC24) for Gilteritinib(0, 0.5, 1, 2, 4, 6, 24 hours post-dose on Days 1 and 28 of cycle 1)
- Ctrough of Erlotinib(Day 8, 15, 22, 28 of cycle 1)
- Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) of Gilteritinib(Predose on Day 1, 3, 8, 15, 22, 28 of cycle 1, Day 1 of cycle 3 and Day 1 of cycle 4)
- AUC24 of Erlotinib(0, 0.5, 1, 2, 4, 6, 24 hours post-dose on Day 28 of cycle 1)
- Objective Response Rate (ORR) in Phase 1b(End of treatment (approximately 4 months))
- Maximum Concentration (Cmax) for Gilteritinib(0, 0.5, 1, 2, 4, 6, 24 hours post-dose on Days 1 and 28 of cycle 1)
- Time After Dosing When Cmax Occurs (Tmax) for Gilteritinib(0, 0.5, 1, 2, 4, 6, 24 hours post-dose on Days 1 and 28 of cycle 1)
- Tmax of Erlotinib(0, 0.5, 1, 2, 4, 6, 24 hours post-dose on Day 28 of cycle 1)