Clinical trial NCT01970865: A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: ALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC
Keywords: Phase 1
Phase 2
safety
pharmacokinetic
pharmacodynamic
efficacy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-10-28
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 .


Eligibility 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 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.

Primary outcomes:
measure: Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1
timeFrame: Cycle 1 (21 days)
measure: Percentage of Participants With Overall and Intracranial Objective Response (Phase 2)
timeFrame: 3 years
Secondary outcomes:
measure: Percentage of Participants With Overall and Intracranial Objective Response (Phase 1)
timeFrame: From start of study treatment until CR or PR (maximum of 8 years approximately)
measure: Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)
timeFrame: From start of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 8 years approximately)
measure: Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1)
timeFrame: 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)
measure: Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1)
timeFrame: 12 and 24 weeks
measure: Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)
timeFrame: 3 years
measure: Progression-Free Survival (PFS) (Phase 1)
timeFrame: 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)
measure: Overall Survival (OS) (Phase 1)
timeFrame: 3 years
measure: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1)
timeFrame: 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.
measure: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
timeFrame: 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).
measure: Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1)
timeFrame: 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.
measure: Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
timeFrame: 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).
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1)
timeFrame: 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.
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1)
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1)
timeFrame: 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.
measure: Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1)
timeFrame: 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.
measure: Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1)
timeFrame: 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)
measure: Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1)
timeFrame: 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.
measure: Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1)
timeFrame: 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)
measure: Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1)
timeFrame: 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.
measure: Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1)
timeFrame: 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)
measure: Renal Clearance (CLr) of PF-06463922 (Phase 1)
timeFrame: 0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
measure: Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1)
timeFrame: 0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
measure: Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1)
timeFrame: 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
measure: Time for Cmax (Tmax) of Midazolam (Phase 1)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1)
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) of Midazolam (Phase 1)
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1)
timeFrame: 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
measure: Terminal Half-Life of Midazolam (Phase 1)
timeFrame: 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
measure: Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 1)
timeFrame: Screening (up to 28 days)
measure: Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 1)
timeFrame: Screening (up to 28 days)
measure: Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)
timeFrame: From start of study treatment until end of treatment (maximum of 8 years approximately)
measure: Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)
timeFrame: From start of study treatment until end of treatment (maximum of 8 years approximately)
measure: Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1)
timeFrame: Baseline, Day 1 of Cycle 1-52, and end of treatment (up to 3 years)
measure: Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study)
timeFrame: 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)
measure: Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy)
timeFrame: 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)
measure: Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy)
timeFrame: Weeks 12 and 24
measure: Time to Progression on the Last Prior Therapy (Phase 2)
timeFrame: From first dose of study treatment to the date of progression (maximum of 7.5 years for Phase 2)
measure: Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy)
timeFrame: 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)
measure: Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2)
timeFrame: From first dose of study treatment until first event of CNS progression (maximum of 7.5 years for Phase 2)
measure: Progression-Free Survival (PFS) (Phase 2 and DDI Substudy)
timeFrame: 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)
measure: Overall Survival (Phase 2 and DDI Substudy)
timeFrame: 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)
measure: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2)
timeFrame: 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
measure: Time for Cmax (Tmax) of PF-06463922 (Phase 2)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2)
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2)
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
measure: Terminal Half-Life of PF-06463922 (Phase 2)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
measure: Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
measure: Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
measure: Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2)
timeFrame: Screening (up to 28 days)
measure: Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2)
timeFrame: Screening (up to 28 days)
measure: Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study)
timeFrame: 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)
measure: Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study)
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study)
timeFrame: 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)
measure: Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology
timeFrame: 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)
measure: Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry
timeFrame: 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)
measure: Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis
timeFrame: 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)
measure: Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
timeFrame: 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)
measure: 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)
timeFrame: 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)
measure: Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
timeFrame: 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)
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2)
timeFrame: From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2)
measure: Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2)
timeFrame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
measure: Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2)
timeFrame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
measure: Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2)
timeFrame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
measure: Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2)
timeFrame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
measure: Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2)
timeFrame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
measure: Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2)
timeFrame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
measure: Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy)
timeFrame: 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)
Other outcomes:
measure: Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study)
timeFrame: 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)
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group/Research
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavillion (AOP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: MDZ: Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Karmanos Center Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Creve Coeur
country: United States
facility: Siteman Cancer Center-West County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-South County
state: Missouri
city: New York
country: United States
facility: Rockefeller Patient Pavilion - Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Rochester Regional Health System
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (Pharmacy)
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Sydney Local Health District [rpa]
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Sydney
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency-Vancouver Centre
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Grenoble Cedex 9
country: France
facility: CHU Grenoble/ Hôpital Albert Michallon
city: Rennes Cedex 9
country: France
facility: CHU de Rennes - Hôpital Pontchaillou - CIC Inserm
city: Rennes Cedex 9
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Toulouse Cedex 9
country: France
facility: Institut Universitaire du Cancer de Toulouse (IUCT-O)
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy (comite poumon-pneumologie)
city: Villejuif
country: France
facility: Institut Gustave Roussy- Pharmacie-Unite Essais Cliniques
city: Cologne
country: Germany
facility: Universitaetsklinik Koeln
city: Shatin
country: Hong Kong
facility: Department of Clinical Oncology, Prince of Wales Hospital
city: Aviano (PN)
country: Italy
facility: Struttura Operativa Complessa Oncologia
city: Milano
country: Italy
facility: Dipartimento di Oncologia Medica, UO Medicina 1Q A, Unita' Nuovi Farmaci e Terapie Innovative
city: Milano
country: Italy
facility: Unita di Farmacologia Clinica e Nuovi Farmaci
city: Perugia
country: Italy
facility: Oncologia Medica
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Akashi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Koto-ku, Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital / Department of Internal Medicine
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National University Hospital Medical Centre
city: Singapore
country: Singapore
facility: National Cancer Center
city: Singapore
country: Singapore
facility: National Cancer Center
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quiron Madrid
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad De Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari de la Vall D'Hebron Edificio General. Planta Baja. UITM. Servicio de Oncologia
city: Lausanne
country: Switzerland
facility: Hospital of Lausanne (CHUV)
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.