Clinical Trials /

Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)

NCT02349633

Description:

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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: B7971001
  • NCT ID: NCT02349633

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PF-06747775Cohort 1
PalbociclibCohort 2A
AvelumabCohort 3

Purpose

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).

Detailed Description

      There remains an unmet medical need to develop EGFR TKI agents that effectively target both
      the single activating mutations of del 19 and L858R, and the secondary resistance mutation
      T790M, while sparing WT EGFR. Drugs active against the resistance mutation will enable
      molecularly targeted therapy with a more favorable toxicity profile than the current standard
      of cytotoxic chemotherapy platinum based doublets. Furthermore, by having a wide margin of
      selectivity favoring the EGFR mutants versus WT EGFR, PF 06747775 is likely to be positioned
      to improve patient outcomes from an efficacy and safety perspective.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalCohort 1 will be initiated (current dose 200 mg)
  • PF-06747775
Cohort 2AExperimentalCohort 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.
  • PF-06747775
  • Palbociclib
Cohort 2BExperimentalCohort 2B will be initiated once the RP2D of the PF-06747775 and palbociclib combination is determined.
  • PF-06747775
  • Palbociclib
Cohort 3ExperimentalCohort 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.
  • PF-06747775
  • Avelumab

Eligibility 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Time Frame: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of Participants With Treatment-emergent AEs (TEAEs) in All Cohorts All Phases (All-causality)
Time Frame:Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)
Safety Issue:
Description: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.
Measure:Number of Participants With TEAEs in All Cohorts All Phases (Treatment-related)
Time Frame:Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)
Safety Issue:
Description: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.
Measure:Number of Participants With Serious Adverse Events (SAEs) in All Cohorts All Phases
Time Frame:Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline up to the end of treatment (maximum of 195 weeks)
Safety Issue:
Description: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.
Measure: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.
Time Frame:Baseline up to Cycle 4 Day 1 (maximum of 10 weeks)
Safety Issue:
Description: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.
Measure: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.
Time Frame:Baseline up to Cycle 4 Day 1 (maximum of 10 weeks)
Safety Issue:
Description: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.
Measure:Number of Participants With Confirmed and Unconfirmed OR in Phase 1 Cohorts
Time Frame:Baseline up to end of treatment (maximum of 195 weeks)
Safety Issue:
Description: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.
Measure:Objective Response Rate (ORR) in Phase 1b/2 Cohorts 2A, 2B and 3
Time Frame:Baseline up to end of treatment (maximum of 108 weeks)
Safety Issue:
Description: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.
Measure:PFS in PF-06747775 200 mg QD Group, Phase 1b Cohorts 2A and 3
Time Frame:Cycle 1 Day 1 up to the end of study (maximum of 5 years)
Safety Issue:
Description: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.
Measure:Duration of Objective Response (DOR) in Phase 1b/2 Cohorts
Time Frame:Baseline up to the end of study (maximum of 5 years)
Safety Issue:
Description: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.
Measure:Overall Survival (OS) Probability at 12 Months in Phase 1b/2 Cohorts
Time Frame:Baseline up to the end of study (maximum of 5 years)
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame:Pre-dose on Cycle 1 Day 11
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure:AUCinf of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study
Time Frame:0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day -8 (+/- 3 days) in lead-in period
Safety Issue:
Description: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.
Measure:Cmax of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study
Time Frame:0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period
Safety Issue:
Description: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.
Measure:CL/F of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study
Time Frame:0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days)
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days)
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days)
Safety Issue:
Description: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.
Measure:AUCtau of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study
Time Frame:Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9
Safety Issue:
Description: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.
Measure:Cmax of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study
Time Frame:Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9
Safety Issue:
Description: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.
Measure:AUCtau of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study
Time Frame:0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21
Safety Issue:
Description: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.
Measure:Cmax of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study
Time Frame:0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21
Safety Issue:
Description: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.
Measure:AUCtau of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study
Time Frame:Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21
Safety Issue:
Description: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.
Measure:Cmax of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study
Time Frame:Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame:Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4
Safety Issue:
Description: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.
Measure:Ctrough of PF-06747775 Following Multiple Doses When Given in Combination With Avelumab on Cycle 1 Day 15 in Phase 1b Cohort 3
Time Frame:Pre-dose on Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame:0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame:Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4
Safety Issue:
Description: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.
Measure: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
Time Frame:Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame:End of infusion of avelumab on Day 1 of Cycles 1-3 and Cycle 1 Day 15
Safety Issue:
Description: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.
Measure:Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations in Tumor Tissue in All Cohorts All Phases
Time Frame:Baseline
Safety Issue:
Description: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.
Measure:Number of Participants With EGFR Mutations in Plasma in All Cohorts All Phases
Time Frame:Baseline
Safety Issue:
Description: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.
Measure:Number of Participants With Positive Serum Anti-drug Antibody (ADA) of Avelumab in Phase 1b Cohort 3
Time Frame:Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure: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
Time Frame: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
Safety Issue:
Description: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.
Measure:AUCtau of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Time Frame: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)
Safety Issue:
Description: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.
Measure:Ctrough of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Time Frame:Pre-dose on Cycle 1 Day 11 (Japan LIC RP2D cohort) and Day 15 (Japan LIC PK cohort)
Safety Issue:
Description: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.
Measure:Rac of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Time Frame: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
Safety Issue:
Description: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.
Measure:Rss of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts
Time Frame: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
Safety Issue:
Description: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.
Measure:CL/F of PF-06747775 Following Single and Multiple Doses in Japan LIC RP2D and PK Cohorts
Time Frame: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
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Pfizer

Trial Keywords

  • EGFRm - Epidermal Growth Factor Receptor Mutation
  • Advanced EGFRm (del19 or L858R +/- T790M NSCLC

Last Updated

June 10, 2021