Phase 1 - open label, multi-center, non-randomized, safety, pharmacokinetic and pharmacodynamics dose escalation study of PF-06459988 as a single agent in patients with advance EGFRm NSCLC (del 19, L858R, +/- T790M). The resulting PF-06459988 dose selected from the phase 1 portion will undergo a series of sub-studies to fully characterize the impact of food, antacid and CYP3A4 inhibitors/inducers. The PK studies are in addition to the MTD expansion and will be completed prior to the initiation of Phase 2. Phase 2 is an open label, multi-center single-arm study of PF-06459988 for the assessment of antitumor activity in patients with advanced EGFRm (del 19 or L858R) NSCLC with T790M.
Name: PF-06459988
Description: The study will evaluate PF-06459988 PO (tablets) continuous daily dosing in 21 day cycles. The starting dose for PF-06459988 will be 50 mg PO daily. The escalation/de-escalation rules will follow the modified toxicity probability interval method with adjustments using the DLT rate and maximum size per dose level of 10 patientsType: DrugSingle agent - study drug
Description: The target probability of DLT at MTD will be 30%
Measure: Number of participants with Dose-limiting toxicities (DLT) (phase 1) Time: up to 21 daysDescription: Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those as noted in the RECIST Criteria: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions
Measure: Number of Participants With Objective Response (phase 2) Time: Time from first dose of study drug to objective response of CR or PR up to 24 monthsDescription: Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those PR are those as noted in the RECIST Criteria: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions
Measure: Number of Participants With Objective Response for those patients with measurable disease (phase 1) Time: time from first dose of study drug until objective response of CR or PR up to 24 monthsDescription: The period from study entry until disease progression, death or date of last contact.
Measure: Progression-Free Survival (PFS) - Phase 2 Time: time from first dose of study drug until Disease Progression or death (whichever first) up to 24 monthsSingle Group Assignment
There are 2 SNPs
A Study For Patients With EGFRm (Epidermal Growth Factor Receptor Mutant) Lung Cancer Phase 1 - open label, multi-center, non-randomized, safety, pharmacokinetic and pharmacodynamics dose escalation study of PF-06459988 as a single agent in patients with advance EGFRm NSCLC (del 19, L858R, +/- T790M). --- L858R ---
The PK studies are in addition to the MTD expansion and will be completed prior to the initiation of Phase 2. Phase 2 is an open label, multi-center single-arm study of PF-06459988 for the assessment of antitumor activity in patients with advanced EGFRm (del 19 or L858R) NSCLC with T790M. --- L858R ---
Progression-Free Survival (PFS) - Phase 2. The period from study entry until disease progression, death or date of last contact.. Inclusion Criteria: - Evidence of histological or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del19 or L858R) NSCLC that is resistant to standard therapy. --- L858R ---
Inclusion Criteria: - Evidence of histological or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del19 or L858R) NSCLC that is resistant to standard therapy. --- L858R ---
Advanced EGFRm (Del 19 or L858R +/- T790M) NSCLC Lung Neoplasms null --- L858R ---
A Study For Patients With EGFRm (Epidermal Growth Factor Receptor Mutant) Lung Cancer Phase 1 - open label, multi-center, non-randomized, safety, pharmacokinetic and pharmacodynamics dose escalation study of PF-06459988 as a single agent in patients with advance EGFRm NSCLC (del 19, L858R, +/- T790M). --- L858R --- --- T790M ---
The PK studies are in addition to the MTD expansion and will be completed prior to the initiation of Phase 2. Phase 2 is an open label, multi-center single-arm study of PF-06459988 for the assessment of antitumor activity in patients with advanced EGFRm (del 19 or L858R) NSCLC with T790M. --- L858R --- --- T790M ---
Advanced EGFRm (Del 19 or L858R +/- T790M) NSCLC Lung Neoplasms null --- L858R --- --- T790M ---