Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Lorlatinib, Lorlatanib
PF-06463922 · 5 trials · 2 indications
Area under the plasma concentration-time profile from time zero extrapolated to infinite time
Maximum plasma concentration
AUCinf is the plasma area under the plasma concentration-time profile from time 0 extrapolated to infinite time. The pharmacokinetics (PK) parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Cmax is the maximum observed plasma concentration. PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
area under plasma concentration-time profile from time 0 extrapolated to infinite time for PF-06463922
observed maximal plasma PF-06463922 concentration
Mass balance: Cumulative recovery (%) of total radioactivity in urine and feces.
Area Under the Curve From Time Zero to Extrapolated Infinite Time
Area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast)
Elimination rate constant
Maximum observed plasma concentration
Time for Cmax
Terminal elimination half life
Apparent oral clearance
Total amount of unchanged drug excreted in the urine from time 0 to discharge day
Total amount of unchanged drug excreted in the urine from time 0 to infinity expressed as percent of dose
Renal Clearance
Total radioactivity in RBCs
Apparent volume of distribution following oral administration
DLT: any of following adverse events (AEs) attributable to PF-06463922: (1) hematologic: grade 4 neutropenia for \>7 days; febrile neutropenia; grade\>=3 neutropenic infection; grade\>=3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade\>=3 pancreatitis; grade\>=3 toxicities (excluding grade \>=3 laboratory abnormalities not requiring dose modifications) persisting after optimal treatment with standard medical therapy; symptomatic grade \>=3 QT interval corrected for heart rate (QTc) prolongation, or asymptomatic grade \>=3 prolongation that had been confirmed by repeat testing, re-evaluation by qualified person, persisted after correction of reversible causes; \>=20% decrease from baseline in left ventricular ejection fraction (LVEF); (3) other: failure to deliver at least 16 out of 21 prescribed daily total dose due to toxicities attributable to study drug; failure to restart dosing after 21 days (1 cycle) delay due to toxicity attributable to study drug.
Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 milliliter (mm) on Target Lesions electronic case report form (eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 percent (%) or more decrease in sum of lesion dimensions (SLD) of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review.
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2. |
| Cohort 2 | EXPERIMENTAL | All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2. |
| Cohort 3 | EXPERIMENTAL | All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2. |
| Cohort 4 | EXPERIMENTAL | All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive the highest safe dose (mg) of PF-06463922 as a single-dose Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2. |
| all subjects | EXPERIMENTAL | subjects will receive a 100 mg single oral dose of PF-06463922 followed by a 100 mg single dose of PF-06463922 combined with 600 mg QD dose of rifampin with at least 10 days of washout period between two PF-06463922 doses. |
| PF-06463922 | EXPERIMENTAL | each subject will receive four single doses of PF-06463922 without food, with food, with rabeprazole (without food), and one of the two new formulations without food. |
| Treatment | EXPERIMENTAL | Radiolabeled PF-06463922 in healthy volunteers |
| Crizotinib | OTHER | ALK+ NSCLC patients who are treatment naïve may be eligible to receive crizotinib following PF-06463922 as a substudy to the main study. |
| Name | Type | Description |
|---|---|---|
| PF-06463922 | DRUG | Single oral dose of PF-06463922 50 mg on Day 1 of Period 1 and Day 5 of Period 2 |
| Itraconazole | DRUG | 200 mg oral dose of itraconazole on Days 1 to 11 during Period 2 |
| rifampin | DRUG | 600 mg QD from day 1 to day 12 in period 2. |
| rabeprazole | DRUG | 20 mg daily tablets in the evening for 5 days and Pf-06463922 on the morning of day 6 in treatment C. |
| [14C] PF-06463922 | DRUG | Single oral dose of 100mg PF-06463922 + \[14C\] PF-06463922 |
| Crizotinib | DRUG | Oral, starting dose of 250 mg BID continuous daily dosing every 21 days |
Inclusion Criteria: * Healthy female subjects of non childbearing potential and/or male subjects, who at the time of screening, are between the ages of 18 and 55 years, inclusive. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs). Exclusion Criteria: * Evide...
Lorlatinib is an investigational small molecule kinase inhibitor being studied for use in ALK-positive anaplastic large cell lymphoma, ALK-positive non-small cell lung cancer (NSCLC), ROS1-positive NSCLC, and moderate hepatic impairment. It is currently in Phase 1 clinical development and is not yet approved by the FDA.
Lorlatinib targets kinases, as it belongs to the -tinib class of kinase inhibitors. It is being investigated for conditions involving ALK and ROS1 alterations, including ALK-positive anaplastic large cell lymphoma and ALK-positive or ROS1-positive non-small cell lung cancer.
Lorlatinib is being developed by Pfizer, Inc., which trades under the ticker symbol PFE on the New York Stock Exchange. The company is conducting clinical trials to evaluate the drug's safety and pharmacokinetics in healthy volunteers and patient populations.
Lorlatinib is in Phase 1 clinical development. All four clinical trials listed for the drug are Phase 1 studies, and none have progressed to later phases. Lorlatinib remains investigational and has not received FDA approval for any indication.
Lorlatinib has been studied in four Phase 1 clinical trials: NCT02564562, NCT02804399, NCT02838264, and NCT03961997. These trials evaluated the drug's absorption, distribution, metabolism, and excretion, as well as its interactions with rifampin, itraconazole, and modafinil in healthy volunteers.
Yes, Lorlatinib is also known as Lorlatanib. Both names refer to the same investigational drug being developed by Pfizer for ALK-positive and ROS1-positive cancers. Researchers and clinicians may use either spelling when referring to this compound.