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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01970865




Registration number
NCT01970865
Ethics application status
Date submitted
16/10/2013
Date registered
28/10/2013
Date last updated
12/08/2024

Titles & IDs
Public title
A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations
Scientific title
PHASE 1/2 STUDY OF PF-06463922 (AN ALK/ROS1 TYROSINE KINASE INHIBITOR) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER HARBORING SPECIFIC MOLECULAR ALTERATIONS
Secondary ID [1] 0 0
2013-002620-17
Secondary ID [2] 0 0
B7461001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - PF-06463922
Treatment: Drugs - Crizotinib

Experimental: PF-06463922 -

Other: Crizotinib - ALK+ NSCLC patients who are treatment naïve may be eligible to receive crizotinib following PF-06463922 as a substudy to the main study.


Treatment: Drugs: PF-06463922
Oral, starting dose 10mg once a day, dose escalation in Phase 1 until recommended Phase 2 dose determined, continuous daily dosing, cycles lasting 21 days

Treatment: Drugs: Crizotinib
Oral, starting dose of 250 mg BID continuous daily dosing every 21 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1
Timepoint [1] 0 0
Cycle 1 (21 days)
Primary outcome [2] 0 0
Percentage of Participants With Overall and Intracranial Objective Response (Phase 2)
Timepoint [2] 0 0
3 years
Secondary outcome [1] 0 0
Percentage of Participants With Overall and Intracranial Objective Response (Phase 1)
Timepoint [1] 0 0
From start of study treatment until CR or PR (maximum of 8 years approximately)
Secondary outcome [2] 0 0
Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)
Timepoint [2] 0 0
From start of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 8 years approximately)
Secondary outcome [3] 0 0
Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1)
Timepoint [3] 0 0
From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately)
Secondary outcome [4] 0 0
Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1)
Timepoint [4] 0 0
12 and 24 weeks
Secondary outcome [5] 0 0
Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)
Timepoint [5] 0 0
3 years
Secondary outcome [6] 0 0
Progression-Free Survival (PFS) (Phase 1)
Timepoint [6] 0 0
From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately)
Secondary outcome [7] 0 0
Overall Survival (OS) (Phase 1)
Timepoint [7] 0 0
3 years
Secondary outcome [8] 0 0
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [8] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [9] 0 0
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [9] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).
Secondary outcome [10] 0 0
Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [10] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [11] 0 0
Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [11] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).
Secondary outcome [12] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [12] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours post-dose on Day -7 for all other groups.
Secondary outcome [13] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [13] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [14] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [14] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [15] 0 0
Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [15] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [16] 0 0
Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [16] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [17] 0 0
Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [17] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [18] 0 0
Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [18] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [19] 0 0
Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [19] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [20] 0 0
Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [20] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [21] 0 0
Renal Clearance (CLr) of PF-06463922 (Phase 1)
Timepoint [21] 0 0
0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
Secondary outcome [22] 0 0
Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1)
Timepoint [22] 0 0
0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
Secondary outcome [23] 0 0
Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1)
Timepoint [23] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [24] 0 0
Time for Cmax (Tmax) of Midazolam (Phase 1)
Timepoint [24] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [25] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1)
Timepoint [25] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [26] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1)
Timepoint [26] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [27] 0 0
Apparent Oral Clearance (CL/F) of Midazolam (Phase 1)
Timepoint [27] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [28] 0 0
Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1)
Timepoint [28] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [29] 0 0
Terminal Half-Life of Midazolam (Phase 1)
Timepoint [29] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [30] 0 0
Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 1)
Timepoint [30] 0 0
Screening (up to 28 days)
Secondary outcome [31] 0 0
Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 1)
Timepoint [31] 0 0
Screening (up to 28 days)
Secondary outcome [32] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)
Timepoint [32] 0 0
From start of study treatment until end of treatment (maximum of 8 years approximately)
Secondary outcome [33] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)
Timepoint [33] 0 0
From start of study treatment until end of treatment (maximum of 8 years approximately)
Secondary outcome [34] 0 0
Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1)
Timepoint [34] 0 0
Baseline, Day 1 of Cycle 1-52, and end of treatment (up to 3 years)
Secondary outcome [35] 0 0
Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study)
Timepoint [35] 0 0
From first dose of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [36] 0 0
Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy)
Timepoint [36] 0 0
From first dose of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [37] 0 0
Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy)
Timepoint [37] 0 0
Weeks 12 and 24
Secondary outcome [38] 0 0
Time to Progression on the Last Prior Therapy (Phase 2)
Timepoint [38] 0 0
From first dose of study treatment to the date of progression (maximum of 7.5 years for Phase 2)
Secondary outcome [39] 0 0
Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy)
Timepoint [39] 0 0
From first dose of study treatment to the first documentation of objective PD (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [40] 0 0
Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2)
Timepoint [40] 0 0
From first dose of study treatment until first event of CNS progression (maximum of 7.5 years for Phase 2)
Secondary outcome [41] 0 0
Progression-Free Survival (PFS) (Phase 2 and DDI Substudy)
Timepoint [41] 0 0
From first dose of study treatment to first documentation of objective PD or death due to any cause, whichever came first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [42] 0 0
Overall Survival (Phase 2 and DDI Substudy)
Timepoint [42] 0 0
From first dose of study treatment until date of death (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [43] 0 0
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2)
Timepoint [43] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [44] 0 0
Time for Cmax (Tmax) of PF-06463922 (Phase 2)
Timepoint [44] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [45] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2)
Timepoint [45] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Secondary outcome [46] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2)
Timepoint [46] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [47] 0 0
Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2)
Timepoint [47] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [48] 0 0
Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2)
Timepoint [48] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Secondary outcome [49] 0 0
Terminal Half-Life of PF-06463922 (Phase 2)
Timepoint [49] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Secondary outcome [50] 0 0
Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2)
Timepoint [50] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [51] 0 0
Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2)
Timepoint [51] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [52] 0 0
Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2)
Timepoint [52] 0 0
Screening (up to 28 days)
Secondary outcome [53] 0 0
Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2)
Timepoint [53] 0 0
Screening (up to 28 days)
Secondary outcome [54] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study)
Timepoint [54] 0 0
From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [55] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study)
Timepoint [55] 0 0
From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [56] 0 0
Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [56] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [57] 0 0
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology
Timepoint [57] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [58] 0 0
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry
Timepoint [58] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [59] 0 0
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis
Timepoint [59] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [60] 0 0
Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [60] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [61] 0 0
Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [61] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [62] 0 0
Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [62] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [63] 0 0
Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2)
Timepoint [63] 0 0
From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2)
Secondary outcome [64] 0 0
Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2)
Timepoint [64] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [65] 0 0
Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2)
Timepoint [65] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [66] 0 0
Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2)
Timepoint [66] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [67] 0 0
Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2)
Timepoint [67] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [68] 0 0
Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2)
Timepoint [68] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [69] 0 0
Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2)
Timepoint [69] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [70] 0 0
Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy)
Timepoint [70] 0 0
From first dose of study treatment to end of treatment maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)

Eligibility
Key inclusion criteria
Inclusion Criteria

* Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA) approved FISH assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by FISH or RT PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT). All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment.
* Disease Status Requirements:

Phase 1: ALK-positive NSCLC and ROS1-positive patients must either be treatment naïve in the advanced setting or have had disease progression after at least 1 previous ALK/ROS1 inhibitor therapy(ies).

Phase 2:

ALK-positive NSCLC patients must either be or have had:

* Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ALK inhibitor therapy allowed).
* Disease progression after crizotinib only. No prior chemotherapy is allowed in the metastatic disease setting.
* Disease progression after crizotinib and 1 or 2 prior regimens of chemotherapy in the metastatic disease setting.
* Disease progression after 1 prior ALK inhibitor therapy other than crizotinib. Patients may have had any number of prior chemotherapy regimens in any disease setting.
* Disease progression after 2 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting.
* Disease progression after 3 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting.

ROS1-positive NSCLC patients may be:

* Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ROS inhibitor therapy).
* Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor therapies).

* Tumor Requirements:

All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients asymptomatic by means of stable or decreasing doses of steroids within the last 2 weeks prior to study entry) will be eligible. Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) are eligible.

* Adequate Bone Marrow, Pancreatic Function, Renal Function and Liver Function.
* Negative Serum pregnancy test for females of childbearing potential
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
* Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
* Systemic anti cancer therapy completed within a minimum of 5 half lives of study entry.
* Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody.
* Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
* Clinically significant cardiovascular disease (that is, active or <3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class = II), second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome.
* History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis.
* Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs that are sensitive CYP2B6 substrates; drugs that are strong CYP2C19 inhibitors; drugs that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/05/2023
Sample size
Target
Accrual to date
Final
364
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Sydney Local Health District [rpa]
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Chris O'Brien Lifehouse - Sydney
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Royal Prince Alfred Hospital - Sydney
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Peter MacCallum Cancer Centre - Melbourne
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Royal Melbourne Hospital - Parkville
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2050 - Sydney Local Health District [rpa]
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2050 - Sydney
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3000 - Melbourne
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3050 - Parkville
Recruitment outside Australia
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Arkansas
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California
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Colorado
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United States of America
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Connecticut
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United States of America
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District of Columbia
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Massachusetts
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Michigan
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Missouri
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Ohio
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Pennsylvania
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Tennessee
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Belgium
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Edegem
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British Columbia
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Canada
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Ontario
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France
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Grenoble Cedex 9
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France
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Rennes Cedex 9
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France
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Toulouse Cedex 9
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France
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Villejuif Cedex
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France
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Villejuif
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Germany
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Cologne
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Hong Kong
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Shatin
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Italy
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Aviano (PN)
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Milano
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Italy
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Perugia
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Aichi
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Chiba
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Ehime
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Hokkaido
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Hyogo
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Japan
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Osaka
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Tokyo
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Fukuoka
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Japan
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Koto-ku, Tokyo
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Korea, Republic of
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Singapore
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Madrid
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Navarra
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Spain
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Barcelona
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Switzerland
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Lausanne
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Switzerland
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Winterthur
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Taiwan
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Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Phase 1 and 2 trial to study the safety, pharmacokinetics, pharmacodynamics, patient reported outcomes and efficacy of PF-06463922 in ALK + advanced non-small cell lung cancer patients and ROS1+ advanced non small cell lung cancer patients .
Trial website
https://clinicaltrials.gov/study/NCT01970865
Trial related presentations / publications
Soo RA, Huat Tan E, Hayashi H, Seto T, Lin CC, Ou SI, Kim DW, Liu G, Abbattista A, Martini JF, Hooi Wong C, Toffalorio F, Solomon BJ. Efficacy and safety of lorlatinib in Asian and non-Asian patients with ALK-positive advanced non-small cell lung cancer: Subgroup analysis of a global phase 2 trial. Lung Cancer. 2022 Jul;169:67-76. doi: 10.1016/j.lungcan.2022.05.012. Epub 2022 May 23.
Ou SI, Solomon BJ, Shaw AT, Gadgeel SM, Besse B, Soo RA, Abbattista A, Toffalorio F, Wiltshire R, Bearz A. Continuation of Lorlatinib in ALK-Positive NSCLC Beyond Progressive Disease. J Thorac Oncol. 2022 Apr;17(4):568-577. doi: 10.1016/j.jtho.2021.12.011. Epub 2022 Jan 10.
Chen J, Ruiz-Garcia A, James LP, Peltz G, Thurm H, Clancy J, Hibma J. Lorlatinib Exposure-Response Analyses for Safety and Efficacy in a Phase I/II Trial to Support Benefit-Risk Assessment in Non-Small Cell Lung Cancer. Clin Pharmacol Ther. 2021 Nov;110(5):1273-1281. doi: 10.1002/cpt.2228. Epub 2021 Jun 26.
Chen J, O'Gorman MT, James LP, Klamerus KJ, Mugundu G, Pithavala YK. Pharmacokinetics of Lorlatinib After Single and Multiple Dosing in Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: Results from a Global Phase I/II Study. Clin Pharmacokinet. 2021 Oct;60(10):1313-1324. doi: 10.1007/s40262-021-01015-z. Epub 2021 May 3.
Peters S, Shaw AT, Besse B, Felip E, Solomon BJ, Soo RA, Bearz A, Gadgeel SM, Lin CC, Kao S, Seto T, Masters ET, Abbattista A, Clancy JS, Thurm H, Reisman A, Peltz G, Ross Camidge D. Impact of lorlatinib on patient-reported outcomes in patients with advanced ALK-positive or ROS1-positive non-small cell lung cancer. Lung Cancer. 2020 Jun;144:10-19. doi: 10.1016/j.lungcan.2020.02.011. Epub 2020 Mar 10.
Bauer TM, Shaw AT, Johnson ML, Navarro A, Gainor JF, Thurm H, Pithavala YK, Abbattista A, Peltz G, Felip E. Brain Penetration of Lorlatinib: Cumulative Incidences of CNS and Non-CNS Progression with Lorlatinib in Patients with Previously Treated ALK-Positive Non-Small-Cell Lung Cancer. Target Oncol. 2020 Feb;15(1):55-65. doi: 10.1007/s11523-020-00702-4.
Shaw AT, Solomon BJ, Chiari R, Riely GJ, Besse B, Soo RA, Kao S, Lin CC, Bauer TM, Clancy JS, Thurm H, Martini JF, Peltz G, Abbattista A, Li S, Ou SI. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019 Dec;20(12):1691-1701. doi: 10.1016/S1470-2045(19)30655-2. Epub 2019 Oct 25.
Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, Chiari R, Bearz A, Lin CC, Gadgeel SM, Riely GJ, Tan EH, Seto T, James LP, Clancy JS, Abbattista A, Martini JF, Chen J, Peltz G, Thurm H, Ou SI, Shaw AT. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018 Dec;19(12):1654-1667. doi: 10.1016/S1470-2045(18)30649-1. Epub 2018 Nov 6. Erratum In: Lancet Oncol. 2019 Jan;20(1):e10. doi: 10.1016/S1470-2045(18)30927-6.
Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. doi: 10.1016/S1470-2045(17)30680-0. Epub 2017 Oct 23.
Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng YL, Liu W, Dardaei L, Frias RL, Schultz KR, Logan J, James LP, Smeal T, Timofeevski S, Katayama R, Iafrate AJ, Le L, McTigue M, Getz G, Johnson TW, Engelman JA. Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F. N Engl J Med. 2016 Jan 7;374(1):54-61. doi: 10.1056/NEJMoa1508887. Epub 2015 Dec 23.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
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Pfizer
Country 0 0
Phone 0 0
Fax 0 0
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Contact person for public queries
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01970865