ALK + advanced non-small cell lung cancer patients and ROS1+ advanced non small cell lung cancer patients .
Conditions
Interventions
investigational material(s)
Generic name etc : Lorlatinib
INN of investigational material : Lorlatinib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigatio
Sponsors
Pfizer R&D Japan G.K.
Eligibility
Sex/Gender
All
Inclusion criteria
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 naive 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 naive (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 naive (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 = II), se
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 = 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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy pharmacokinetics Percentage of Participants With Overall and Intracranial Objective Response (Phase 1) Time to Tumor Response (TTR) and Intracranial TTR (Phase 1) Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1) Progression-Free Survival (PFS) (Phase 1) Overall Survival (OS) (Phase 1) Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) Renal Clearance (CLr) of PF-06463922 (Phase 1) Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) ( | — |
Countries
Asia except Japan, Europe, Japan, North America, Oceania
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed