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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02349633
Registration number
NCT02349633
Ethics application status
Date submitted
23/01/2015
Date registered
29/01/2015
Date last updated
10/06/2021
Titles & IDs
Public title
Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)
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Scientific title
PHASE 1/2 OPEN-LABEL STUDY OF PF-06747775 (EPIDERMAL GROWTH FACTOR RECEPTOR T790M INHIBITOR) IN PATIENTS WITH ADVANCED EPIDERMAL GROWTH FACTOR RECEPTOR MUTANT (DEL 19 OR L858R ± T790M) NON-SMALL CELL LUNG CANCER
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Secondary ID [1]
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B7971001
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer
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Condition category
Condition code
Cancer
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Lung - Mesothelioma
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Cancer
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Lung - Non small cell
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Cancer
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Lung - Small cell
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - PF-06747775
Treatment: Drugs - Palbociclib
Treatment: Drugs - Avelumab
Experimental: Cohort 1 - Cohort 1 will be initiated (current dose 200 mg)
Experimental: Cohort 2A - Cohort 2A will evaluate PF-06747775 200 mg by mouth (PO) daily (QD) in combination with palbociclib continuous PO QD dosing in 21-day cycles. The starting dose (DL1) for palbociclib will be 100 mg PO daily. Dose finding will follow mTPI method with adjustments using DLT rate.
Experimental: Cohort 2B - Cohort 2B will be initiated once the RP2D of the PF-06747775 and palbociclib combination is determined.
Experimental: Cohort 3 - Cohort 3 combination is PF-06747775 200 mg PO QD and avelumab 10 mg/kg IV Q2W in 28-day (4-week) cycles. Dose finding will follow the mTPI design. Once RP2D of PF-06747775 in combination with avelumab is determined, the Dose Expansion Phase will be opened.
Treatment: Drugs: PF-06747775
Treatment: Drugs: Palbociclib
Treatment: Drugs: Avelumab
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Dose Limiting Toxicities (DLTs) During the First Cycle in Phase 1 Dose-escalation Cohorts, Japan LIC and Phase 1b Cohort 3, and First 2 Cycles in Phase 1b Cohort 2A
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Assessment method [1]
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DLT was defined as any of the following adverse events (AEs) occurring during the first cycle for Phase 1 dose-escalation cohorts, Japan LIC and Phase 1b Cohort 3, or the first 2 cycles for Phase 1b Cohort 2A of treatment, and considered attributable to study intervention: Grade 4 neutropenia >7 days; febrile neutropenia; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade >=3 non-hematologic toxicities; Grade 4 rash, mucositis, or diarrhea; failure to receive at least 70% of planned doses; Grade 3 QTcF prolongation in asymptomatic participants; treatment-related AEs attributable to PF-06747775, palbociclib or both that caused palbociclib treatment delay >= 10 days or omission of at least 12 doses of the combination. Grade of AE was defined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
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Timepoint [1]
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21 days for Phase 1 dose-escalation cohorts and Japan LIC; 42 days for Phase 1b Cohort 2A; 28 days for Phase 1b Cohort 3
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Primary outcome [2]
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Number of Participants With Confirmed Objective Response (OR) in PF-06747775 200 mg QD Group
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Assessment method [2]
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Number of participants with confirmed OR according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. Complete response (CR) was defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.
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Timepoint [2]
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Baseline up to end of treatment (maximum of 165 weeks)
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Primary outcome [3]
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Progression-free Survival (PFS) in Phase 2 Cohort 2B
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Assessment method [3]
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PFS was based on Kaplan-Meier estimates. PFS was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective progression (PD) or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
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Timepoint [3]
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Cycle 1 Day 1 up to the end of study (maximum of 5 years)
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Secondary outcome [1]
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Number of Participants With Treatment-emergent AEs (TEAEs) in All Cohorts All Phases (All-causality)
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Assessment method [1]
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AE = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events = death related to an AE. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
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Timepoint [1]
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Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)
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Secondary outcome [2]
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Number of Participants With TEAEs in All Cohorts All Phases (Treatment-related)
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Assessment method [2]
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Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events = death related to an AE. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Treatment-related AEs were determined by the investigator.
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Timepoint [2]
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Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)
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Secondary outcome [3]
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Number of Participants With Serious Adverse Events (SAEs) in All Cohorts All Phases
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Assessment method [3]
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An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related SAEs were determined by the investigator.
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Timepoint [3]
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Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)
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Secondary outcome [4]
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Number of Participants With Shifts of Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline in All Cohorts All Phases
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Assessment method [4]
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Laboratory values included hemoglobin, platelets, white blood cell count (WBC), absolute (abs) neutrophils, abs lymphocytes, abs monocytes, abs eosinophils, abs basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (Alk Phos), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate, prothrombin time (PT) or international normalized ratio (INR), partial thromboplastin time (PTT), urinalysis and pregnancy test. Grades of laboratory results were defined by NCI CTCAE version 4.03. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death.
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Timepoint [4]
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Baseline up to the end of treatment (maximum of 195 weeks)
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Secondary outcome [5]
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Number of Participants Meeting Categorical Criteria of QTcF Values When PF-06747775 Was Given as a Single Agent, and in Combination With Palbociclib and Avelumab.
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Assessment method [5]
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Number of participants meeting categorical criteria of QTcF values when PF-06747775 was given as a single agent in Phase 1 dose-escalation cohorts, PF-06747775 200 mg QD group (only participants in Phase 2 Cohort 1 and Japan LIC were eligible for QTcF within this combined group), and in combination with palbociclib and avelumab in Phase 1b/2 Cohorts 2A, 2B and 3. Criteria for categorization of QTcF were defined as: maximum values 450 - <480 msec, 480 - <500 msec and >=500 msec.
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Timepoint [5]
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Baseline up to Cycle 4 Day 1 (maximum of 10 weeks)
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Secondary outcome [6]
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Number of Participants Meeting Categorical Criteria of QTcB Values When PF-06747775 Was Given as a Single Agent, and in Combination With Palbociclib and Avelumab.
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Assessment method [6]
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Number of participants meeting categorical criteria of QTcB values when PF-06747775 was given as a single agent in Phase 1 dose-escalation cohorts, PF-06747775 200 mg QD group (only participants in Phase 2 Cohort 1 and Japan LIC were eligible for QTcB within this combined group), and in combination with palbociclib and avelumab in Phase 1b/2 Cohorts 2A, 2B and 3. Criteria for categorization of QTcB were defined as: maximum values 450 - <480 msec, 480 - <500 msec and >=500 msec.
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Timepoint [6]
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Baseline up to Cycle 4 Day 1 (maximum of 10 weeks)
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Secondary outcome [7]
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Number of Participants With Confirmed and Unconfirmed OR in Phase 1 Cohorts
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Assessment method [7]
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Number of participants in Phase 1 cohorts with confirmed and unconfirmed OR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable was defined as not qualifying for CR, PR or PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. Indeterminate was defined as progression not documented.
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Timepoint [7]
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Baseline up to end of treatment (maximum of 195 weeks)
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Secondary outcome [8]
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Objective Response Rate (ORR) in Phase 1b/2 Cohorts 2A, 2B and 3
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Assessment method [8]
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ORR was defined as percentage of participants with OR based assessment of CR or PR according to RECIST v1.1 that must have been confirmed =4 weeks later. Participants who did not have an on treatment radiographic tumor assessment due to early progression, who received anti tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non responders in the assessment of ORR. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.
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Timepoint [8]
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Baseline up to end of treatment (maximum of 108 weeks)
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Secondary outcome [9]
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PFS in PF-06747775 200 mg QD Group, Phase 1b Cohorts 2A and 3
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Assessment method [9]
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PFS was based on Kaplan-Meier estimates. PFS was defined as the time from Cycle 1 Day 1 to the date of the first documentation of PD or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
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Timepoint [9]
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Cycle 1 Day 1 up to the end of study (maximum of 5 years)
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Secondary outcome [10]
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Duration of Objective Response (DOR) in Phase 1b/2 Cohorts
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Assessment method [10]
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DOR was the time from the date of first documentation of confirmed CR or PR to the date of first documentation of PD or death due to any cause. If tumor progression data included more than 1 date, the first date was used. DOR (months) = [progression/death date - first date of OR + 1]/30.4. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable was defined as not qualifying for CR, PR or PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
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Timepoint [10]
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Baseline up to the end of study (maximum of 5 years)
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Secondary outcome [11]
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Overall Survival (OS) Probability at 12 Months in Phase 1b/2 Cohorts
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Assessment method [11]
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OS probability was based on Kaplan-Meier method. OS was defined as the time from the start date to date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.
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Timepoint [11]
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Baseline up to the end of study (maximum of 5 years)
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Secondary outcome [12]
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Plasma Area Under the Curve From Zero to Infinite Time (AUCinf) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1
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Assessment method [12]
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Plasma area under the curve from zero to infinite time (AUCinf) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
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Timepoint [12]
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1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1
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Secondary outcome [13]
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Maximum Concentration Observed After Dose Administration (Cmax) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1
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Assessment method [13]
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Cmax of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. Cmax was the maximum concentration after dose administration observed directly from the data.
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Timepoint [13]
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1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1
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Secondary outcome [14]
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Half-life (t1/2) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1
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Assessment method [14]
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Half-life (t1/2) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. t1/2 was defined as the time measured for the plasma concentration to decrease by one half.
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Timepoint [14]
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1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1
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Secondary outcome [15]
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Apparent Clearance (CL/F) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1
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Assessment method [15]
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Apparent clearance (CL/F) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
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Timepoint [15]
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1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1
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Secondary outcome [16]
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Volume of Distribution (Vz/F) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1
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Assessment method [16]
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Vz/F was defined as apparent volume of distribution. Vz/F was calculated as: Vz/F = dose / (AUCinf * kel). kel was defined as terminal phase rate constant and calculated by a linear regression of the log-linear concentration-time curve. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
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Timepoint [16]
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1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1
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Secondary outcome [17]
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Pre-dose Concentration at Steady State (Ctrough) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B
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Assessment method [17]
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Pre-dose concentration at steady state (Ctrough) of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data.
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Timepoint [17]
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Pre-dose on Cycle 1 Day 11
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Secondary outcome [18]
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Area Under the Curve at Steady State (AUCtau) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B
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Assessment method [18]
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AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
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Timepoint [18]
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0 (pre-dose), 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 11 for Phase 1 dose-escalation cohorts; 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose on Cycle 1 Day 11 for Phase 2 Cohorts 1 and 2B
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Secondary outcome [19]
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CL/F of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B
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Assessment method [19]
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CL/F of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. CL/F was calculated as: CL/F = dose / AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
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Timepoint [19]
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0 (pre-dose), 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 11 for Phase 1 dose-escalation cohorts; 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose for Phase 2 Cohorts 1 and 2B
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Secondary outcome [20]
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Observed Accumulation Ratio (Rac) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B
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Assessment method [20]
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Rac was calculated as: Rac = (steady state AUCtau) / (single dose AUC24). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. AUC24 was defined as area under the plasma concentration-time curve from time 0 to 24 hours.
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Timepoint [20]
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1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -8 (dose-escalation cohorts) or -4 (Cohort 1); 0 (pre-dose), 1, 2, 4, 6, 8 (except for Cohort 1) and 24 hours post dose on Cycle 1 Day 11 for dose-escalation cohorts, Cohorts 1 and 2B
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Secondary outcome [21]
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Steady State Accumulation Ratio (Rss) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B
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Assessment method [21]
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Steady state accumulation ratio (Rss) of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. Rss was calculated as: Rss = (steady state AUCtau) / (single dose AUCinf). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
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Timepoint [21]
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1, 2, 4, 6, 8, 24, 48 and 72 hours post dose on Lead-in Day -8 (dose-escalation cohorts) or Day -4 (Cohort 1); 0 (pre-dose), 1, 2, 4, 6, 8 (except for Cohort 1) and 24 hours post dose on Cycle 1 Day 11
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Secondary outcome [22]
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AUCinf of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study
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Assessment method [22]
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AUCinf of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period in Phase 1 Sildenafil sub-study. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time.
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Timepoint [22]
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0
0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day -8 (+/- 3 days) in lead-in period
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Secondary outcome [23]
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0
Cmax of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study
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Assessment method [23]
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Cmax values for sildenafil were analyzed using a mixed effects model with treatment as fixed effect and participant as random effect to estimate the effect of steady state PF-06747775 on sildenafil exposure. Cmax was the maximum concentration after dose administration observed directly from the data.
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Timepoint [23]
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0
0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period
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Secondary outcome [24]
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0
CL/F of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study
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Assessment method [24]
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CL/F of sildenafil dosed alone on Day -8 lead-in period in Phase 1 Sildenafil sub-study. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
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Timepoint [24]
0
0
0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period
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Secondary outcome [25]
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0
AUCinf of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study
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Assessment method [25]
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0
AUCinf of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period in Phase 1 Sildenafil sub-study. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time.
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Timepoint [25]
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0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days)
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Secondary outcome [26]
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0
Cmax of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study
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Assessment method [26]
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0
Cmax values for sildenafil were analyzed using a mixed effects model with treatment as fixed effect and participant as random effect to estimate the effect of steady state PF-06747775 on sildenafil exposure.
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Timepoint [26]
0
0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days)
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Secondary outcome [27]
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0
CL/F of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study
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Assessment method [27]
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0
CL/F of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period and Cycle 1 Day 11 in Phase 1 Sildenafil sub-study. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
Query!
Timepoint [27]
0
0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days)
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Secondary outcome [28]
0
0
AUCtau of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study
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Assessment method [28]
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0
AUCtau of PF-06747775 at the RP2D under fed and overnight fasted conditions in Phase 1 Food Effect and Rifampin DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [28]
0
0
Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9
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Secondary outcome [29]
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0
Cmax of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study
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Assessment method [29]
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0
Cmax of PF-06747775 at the RP2D under fed and overnight fasted conditions in Phase 1 Food Effect and Rifampin DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data.
Query!
Timepoint [29]
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0
Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9
Query!
Secondary outcome [30]
0
0
AUCtau of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study
Query!
Assessment method [30]
0
0
AUCtau of PF-06747775 at the RP2D when dosed alone and after esomeprazole/itraconazole treatment in Phase 1 Esomeprazole-Itraconazole DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [30]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21
Query!
Secondary outcome [31]
0
0
Cmax of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study
Query!
Assessment method [31]
0
0
Cmax of PF-06747775 at RP2D when dosed alone and after esomeprazole/itraconazole treatment in Phase 1 Esomeprazole-Itraconazole DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data.
Query!
Timepoint [31]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21
Query!
Secondary outcome [32]
0
0
AUCtau of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study
Query!
Assessment method [32]
0
0
AUCtau of PF-06747775 at RP2D dosed alone and after rifampin treatment in Phase 1 Food Effect and Rifampin DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [32]
0
0
Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21
Query!
Secondary outcome [33]
0
0
Cmax of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study
Query!
Assessment method [33]
0
0
Cmax of PF-06747775 at RP2D dosed alone and after rifampin treatment in Phase 1 Food Effect and Rifampin DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data.
Query!
Timepoint [33]
0
0
Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21
Query!
Secondary outcome [34]
0
0
AUCtau of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B
Query!
Assessment method [34]
0
0
AUCtau of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [34]
0
0
0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Query!
Secondary outcome [35]
0
0
Cmax of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B
Query!
Assessment method [35]
0
0
Cmax of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Cmax was the maximum concentration after dose administration observed directly from the data.
Query!
Timepoint [35]
0
0
0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Query!
Secondary outcome [36]
0
0
CL/F of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B
Query!
Assessment method [36]
0
0
CL/F of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. CL/F was calculated as: CL/F = dose / AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [36]
0
0
0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Query!
Secondary outcome [37]
0
0
Ctrough of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B
Query!
Assessment method [37]
0
0
Ctrough of PF-06747775 following multiple doses when given in combination with palbociclib on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data.
Query!
Timepoint [37]
0
0
Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4
Query!
Secondary outcome [38]
0
0
Ctrough of PF-06747775 Following Multiple Doses When Given in Combination With Avelumab on Cycle 1 Day 15 in Phase 1b Cohort 3
Query!
Assessment method [38]
0
0
Ctrough of PF-06747775 following multiple doses when given in combination with avelumab on Cycle 1 Day 15 in Phase 1b Cohort 3. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data.
Query!
Timepoint [38]
0
0
Pre-dose on Cycle 1 Day 15
Query!
Secondary outcome [39]
0
0
AUCtau of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B
Query!
Assessment method [39]
0
0
AUCtau of palbociclib following multiple doses when given in combination with PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [39]
0
0
0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Query!
Secondary outcome [40]
0
0
Cmax of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B
Query!
Assessment method [40]
0
0
Cmax of palbociclib following multiple doses when given in combination with PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Cmax was the maximum concentration after dose administration observed directly from the data.
Query!
Timepoint [40]
0
0
0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Query!
Secondary outcome [41]
0
0
Ctrough of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B
Query!
Assessment method [41]
0
0
Ctrough of palbociclib following multiple doses when given in combination with PF-06747775 on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b/2 Cohorts 2A and 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data.
Query!
Timepoint [41]
0
0
Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4
Query!
Secondary outcome [42]
0
0
Ctrough of Avelumab When Given in Combination With PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3
Query!
Assessment method [42]
0
0
Ctrough of avelumab when given in combination with PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data.
Query!
Timepoint [42]
0
0
Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15
Query!
Secondary outcome [43]
0
0
Cmax of Avelumab When Given in Combination With PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3
Query!
Assessment method [43]
0
0
Cmax of avelumab when given in combination with PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. Cmax was the end of infusion peak concentration observed directly from data.
Query!
Timepoint [43]
0
0
End of infusion of avelumab on Day 1 of Cycles 1-3 and Cycle 1 Day 15
Query!
Secondary outcome [44]
0
0
Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations in Tumor Tissue in All Cohorts All Phases
Query!
Assessment method [44]
0
0
Number of participants with EGFR mutations in tumor tissue in all cohorts all phases. EGFR mutation assessments in tumor tissue included the mutations statuses of exon 19 deletion (del 19), exon 21 (L858R), G719X, L861Q, S768I, exon 20 insertions and T790M.
Query!
Timepoint [44]
0
0
Baseline
Query!
Secondary outcome [45]
0
0
Number of Participants With EGFR Mutations in Plasma in All Cohorts All Phases
Query!
Assessment method [45]
0
0
Number of participants with EGFR mutations in plasma in all cohorts all phases. EGFR mutation assessments in plasma included the mutations statuses of exon 19 deletion (del 19), exon 21 (L858R) and T790M.
Query!
Timepoint [45]
0
0
Baseline
Query!
Secondary outcome [46]
0
0
Number of Participants With Positive Serum Anti-drug Antibody (ADA) of Avelumab in Phase 1b Cohort 3
Query!
Assessment method [46]
0
0
Number of participants with positive serum ADA of avelumab at pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3.
Query!
Timepoint [46]
0
0
Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15
Query!
Secondary outcome [47]
0
0
AUCinf of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort
Query!
Assessment method [47]
0
0
AUCinf of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time.
Query!
Timepoint [47]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort
Query!
Secondary outcome [48]
0
0
Cmax of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort
Query!
Assessment method [48]
0
0
Cmax of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. Cmax was the maximum concentration observed from data.
Query!
Timepoint [48]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort
Query!
Secondary outcome [49]
0
0
Vz/F of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort
Query!
Assessment method [49]
0
0
Vz/F of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. Vz/F was defined as apparent volume of distribution. Vz/F was calculated as: Vz/F = dose / (AUCinf * kel). kel was defined as terminal phase rate constant and calculated by a linear regression of the log-linear concentration-time curve. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
Query!
Timepoint [49]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort
Query!
Secondary outcome [50]
0
0
t1/2 of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort
Query!
Assessment method [50]
0
0
t1/2 of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. t1/2 was defined as the time measured for the plasma concentration to decrease by one half.
Query!
Timepoint [50]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort
Query!
Secondary outcome [51]
0
0
AUCtau of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Query!
Assessment method [51]
0
0
AUCtau of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [51]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Cycle 1 Day 11 (Japan LIC RP2D cohort) and Day 15 (Japan LIC PK cohort)
Query!
Secondary outcome [52]
0
0
Ctrough of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Query!
Assessment method [52]
0
0
Ctrough of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data.
Query!
Timepoint [52]
0
0
Pre-dose on Cycle 1 Day 11 (Japan LIC RP2D cohort) and Day 15 (Japan LIC PK cohort)
Query!
Secondary outcome [53]
0
0
Rac of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Query!
Assessment method [53]
0
0
Rac of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. Rac was calculated as: Rac = (steady state AUCtau) / (single dose AUC24). AUC24 was defined as area under the plasma concentration-time curve from time 0 to 24 hours following single dose. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours.
Query!
Timepoint [53]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Cycle 1 Days 1 and 15 for Japan LIC PK cohort
Query!
Secondary outcome [54]
0
0
Rss of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Query!
Assessment method [54]
0
0
Rss of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan RP2D cohort and Cycle 1 Day 15 in Japan PK cohort. Rss was calculated as: Rss = (steady state AUCtau) / (single dose AUCinf). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
Query!
Timepoint [54]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Cycle 1 Days 1 and 15 for Japan LIC PK cohort
Query!
Secondary outcome [55]
0
0
CL/F of PF-06747775 Following Single and Multiple Doses in Japan LIC RP2D and PK Cohorts
Query!
Assessment method [55]
0
0
CL/F of PF-06747775 following single dose on Lead-in Day -4 in Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK cohort, and following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and on Cycle 1 Day 15 in Japan LIC PK cohort. CL/F was calculated as: CL/F = dose/AUCinf for single dose or dose/AUCtau for multiple doses. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time.
Query!
Timepoint [55]
0
0
0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Lead-in Day-7, Days 1 and 15 for Japan LIC PK cohort
Query!
Eligibility
Key inclusion criteria
Partial Inclusion criteria:
Evidence of histologically or cytologically confirmed diagnosis of locally advanced or
metastatic EGFRm (del 19 or L858R) NSCLC:
1. As detected by local EGFR mutation test that includes QIAGEN therascreen EGFR RGQ PCR
kit, Roche cobas® EGFR Mutation Test or a sponsor-approved laboratory developed test
that is validated in a CLIA laboratory (with tissue submitted for central laboratory
confirmation via FDA approved QIAGEN therascreen RCQ PCR kit).
2. T790M disease as follows:
Phase 1 If a repeat biopsy was performed on the tumor following prior EGFR TKI
therapy, then T790M positive disease must be present. Patients of unknown T790M status
following EGFR TKI progression (ie, no post EGFR TKI progression biopsy was performed)
are eligible.
In the PK sub-studies involving food/antacid and CYP3A4 effects, patients with EGFRm
(del 19 or L858R) with any T790M status are eligible to enroll.
Studies at RP2D Cohort 1: Patients may have de novo T790M mutation, but it is not
required. Cohort 2 and Cohort 3: Patients must have EGRFm (del 19 AND T790M or L858R
AND T790M) NSCLC tumors as detected by local EGFR mutation test that includes QIAGEN
Therascreen EGFR RGQ PCR kit, Roche cobas® EGFR Mutation Test or a sponsor-approved
laboratory developed test that is validated in a CLIA laboratory, which will then be
retrospectively confirmed by the central validated Thermo Fisher Scientific Oncomine
Next Generation Sequencing (NGS) cancer panel test. Patients will also be enrolled if
they solely test positive for EGFR (del 19 AND T790M or L858R AND T790M) NSCLC in
plasma detected by local EGFR mutation test that includes QIAGEN Therascreen EGFR
Plasma RGQ kit, Roche cobas® EGFR mutation test v2 (US-IVD) or Sysmex Inostic's
OncoBEAMTM EGFR test or a sponsor-approved laboratory developed test that is validated
in a CLIA laboratory, which will then be retrospectively confirmed by a validated
cfDNA test as determined by the Sponsor.
3. Prior treatment for EGFRm NSCLC as follows:
Phase 1 Has progressed after at least 1 prior line of therapy including and EGFR TKI.
Patients may have also received other lines of therapy before or after the EGFR TKI.
Studies at RP2D Cohort 1: no prior treatment for locally advanced or metastatic EGFRm
NSCLC. Cohorts 2 and 3: must have had disease progression on treatment with an approved 1st
or 2nd generation EGFR TKI. Patients who have been treated with a 3rd generation EGFR TKI
are ineligible for this study. Patients may have had multiple lines of therapy; however,
the last therapy prior to study treatment must have been an approved EGFR TKI and received
within 6 weeks prior to study registration.
Patients must have at least one measurable lesion as defined by RECIST version 1.1 that has
not been previously irradiated.
Tumor tissue available. Requesting formalin fixed paraffin embedded (FFPE) block or 15
unstained sections (5 micron). If a lesser amount of tissue is available, contact the
sponsor. An archival specimen is acceptable for Phase 1; a de novo specimen is required for
Cohorts 2, and 3 if the T790M status was confirmed by tissue biopsy.
Partial
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
For All Phases/Cohorts Previously diagnosed brain metastases, unless the patient has
completed the treatment that is clinically indicated, if any, and has recovered from the
acute effects of any treatment that was delivered prior to study registration, have
discontinued corticosteroid treatment for these metastases prior to registration, and are
neurologically stable.
Major surgery within 2 weeks prior to registration.
Radiation therapy, excluding stereotactic radiosurgery (SRS), within 1 week prior to
registration.
Systemic anti cancer therapy within 2 weeks or 5 half-lives (whichever is longer) of
registration excluding EGFR TKIs. Patients on EGFR TKIs must discontinue the agent for a
minimum of:
- 2 days prior to registration for erlotinib or afatinib, or 3 days for gefitinib if
they will be part of the lead-in single dose PF-06747775 PK study (Phase 1 Dose
Escalation Single and Multiple dose PK and ECG Assessments; Phase 1 Sildenafil at MTD;
and Phase 1b/2 First-Line Single Agent). Please contact the Sponsor for direction for
any other EGFR TKI.
- 5 half-lives or 5 days (whichever is longer) prior to registration if they will be
starting on continuous PF-06747775 dosing directly (Phase 1 PK sub-studies at RP2D;
Phase 1b/2 Combination with Palbociclib; Phase 1b Combination with Avelumab).
Partial Exclusions for Cohort 2A and 2B (Palbociclib combo):
Prior treatment with a CDK 4/6 inhibitor.
Partial Exclusions for Cohort 3 (Avelumab combo):
Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T
lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or
any other antibody or drug specifically targeting T cell co stimulation or immune
checkpoint pathways).
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not
requiring immunosuppressive treatment are eligible
Use of immunosuppressive medication at time of randomization
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1/Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
14/05/2015
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
28/05/2020
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
65
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Query!
Recruitment hospital [1]
0
0
Chris O'Brien Lifehouse - Camperdown
Query!
Recruitment hospital [2]
0
0
Royal Prince Alfred Hospital - Camperdown
Query!
Recruitment hospital [3]
0
0
Prince Charles Hospital, Cancer Care Services - Chermside
Query!
Recruitment postcode(s) [1]
0
0
2050 - Camperdown
Query!
Recruitment postcode(s) [2]
0
0
4032 - Chermside
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Connecticut
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Pennsylvania
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Washington
Query!
Country [5]
0
0
Japan
Query!
State/province [5]
0
0
Ehime
Query!
Country [6]
0
0
Japan
Query!
State/province [6]
0
0
Koto-ku, Tokyo
Query!
Country [7]
0
0
Korea, Republic of
Query!
State/province [7]
0
0
Seoul
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Pfizer
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This is a Phase 1/2 study of PF-06747775 as a single agent and in combination with other
cancer treatments in patients with advanced EGFRm NSCLC. The overall clinical study consists
of a Phase 1 single agent dose-escalation and expansion part to determine the RP2D of
PF-06747775 single agent in patients with previously-treated EGFRm NSCLC followed by
sequential evaluations of PF-06747775 at the RP2D in 3 different clinical scenarios as
detailed below:
- Cohort 1: Phase 2 evaluation of PF-06747775 as a single agent in previously untreated
patients with advanced EGFRm NSCLC,
- Cohort 2: Phase 1b single arm evaluation of PF-06747775 in combination with palbociclib
(Cohort 2A) followed by Phase 2 randomized evaluation of PF 06747775 in combination with
palbociclib vs PF-06747775 single agent (Cohort 2B) in previously-treated patients with
EGFRm NSCLC with a secondary T790M mutation (del 19 and T790M or L858R and T790M), and
- Cohort 3: Phase 1b evaluation of PF-06747775 in combination with avelumab in
previously-treated patients with EGFRm NSCLC with a secondary T790M mutation (del 19 and
T790M or L858R and T790M).
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT02349633
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Pfizer CT.gov Call Center
Query!
Address
0
0
Pfizer
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
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Contact person for public queries
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Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02349633
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