Analysis of the Effectiveness and Safety of Lorlatinib in Untreated ALK-Positive NSCLC Patients in a French Real-World Context (LOREA)

May 5, 2026 updated by: Pfizer

LOREA : ANALYSIS OF THE EFFECTIVENESS AND SAFETY OF LORLATINIB IN UNTREATED ALK-POSITIVE NSCLC PATIENTS IN A FRENCH NON INTERVENTIONAL STUDY

Analysis of the Effectiveness and Safety of Lorlatinib in Untreated ALK-Positive NSCLC Patients in a French Real-World context

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Aix-en-Provence, France, 13100
        • Recruiting
        • Centre Hospitalier du Pays d AIX
      • Albi, France, 81000
        • Recruiting
        • CH ALBI
      • Amiens, France, 80000
        • Recruiting
        • CHU Amiens Sud
      • Avignon, France, 84000
        • Not yet recruiting
        • CH Avignon
      • Bordeaux, France, 33076
        • Not yet recruiting
        • Institut Bergonie
      • Bordeaux, France, 30072
        • Not yet recruiting
        • Polyclinique Bordeaux Nord Aquitaine
      • Brest, France, 29000
        • Not yet recruiting
        • Hopital Morvan
      • Créteil, France, 94010
        • Recruiting
        • CHIC
      • Dijon, France, 21000
        • Recruiting
        • Clcc Georges Francois Leclerc
      • Gleizé, France, 69400
        • Not yet recruiting
        • Hopital de Villefranche Sur Saone
      • Limoges, France, 87042
        • Recruiting
        • CHU Limoges
      • Lyon, France, 69373
        • Not yet recruiting
        • Centre Léon Bérard
      • Metz, France, 57070
        • Recruiting
        • Hopital Robert Schuman de Vantoux
      • Nancy, France, 54035
        • Not yet recruiting
        • CHRU de Nancy
      • Nantes, France, 44093
        • Recruiting
        • CHU Nantes
      • Paris, France, 75014
        • Not yet recruiting
        • Hôpital Cochin
      • Paris, France, 75908
        • Recruiting
        • Hôpital Europeén Georges Pompidou
      • Paris, France, 75674
        • Recruiting
        • Hopital Saint Joseph
      • Pau, France, 64046
        • Recruiting
        • Centre Hospitalier Francois Mitterand
      • Pringy, France, 74374
        • Recruiting
        • CH Annecy Genevois
      • Quimper, France, 29107
        • Recruiting
        • Ch Cornouaille
      • Reims, France, 51056
        • Recruiting
        • Institut Godinot
      • Rennes, France, 35033
        • Recruiting
        • Hôpital Pontchaillou
      • Suresnes, France, 92151
        • Recruiting
        • Hôpital Foch
      • TSA 50032 Toulouse, France, 31059
        • Recruiting
        • Hôpital de Rangueil
      • Toulon, France, 83000
        • Not yet recruiting
        • Chits Ch Sainte Musse
      • Tours, France, 37000
        • Recruiting
        • CHRU Bretonneau
      • Troyes, France, 10003
        • Recruiting
        • CH Troyes
      • Valenciennes, France, 59300
        • Recruiting
        • Clinique Teissier
      • Vannes, France, 56017
        • Recruiting
        • CHBA
    • Paris
      • Paris, Paris, France, 75005
        • Recruiting
        • Institut Curie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Study Population

ALK-positive locally advanced or metastatic NSCLC patients adults for whom Lorlatinib was initiated in first line.

Description

Inclusion Criteria: Participants are eligible to be included in the study only if all the following criteria apply:

  • Patients (male or female) 18 years of age or older at age inclusion
  • Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic (TNM 8th classification) ALK-positive NSCLC (IHC 3+/FISH positive/transcriptomic method)
  • Complete radiological evaluation has to be performed before the start of lorlatinib by contrast enhanced CT-scan of thorax and upper abdomen and brain MRI, as per routine care
  • Patients with ECOG performance status grade 0, 1, or 2

Exclusion Criteria: Participants are excluded from the study if any of the following criteria Apply

  • Evidence of active malignancy within the last 2 years prior to inclusion (other than NSCLC, non-melanoma skin cancer, cervical in situ cancer, papillary thyroid cancer, lobular carcinoma in situ/ductal carcinoma in situ (LCIS/DCIS) of the breast, or localized prostate cancer).
  • Patients who have previously received adjuvant ALK TKI therapy (unless metastatic relapse occurs more than one year after completion of adjuvant therapy).
  • Patients who have previously received systemic NSCLC therapy in metastatic condition.

  • Patients using any of the following food or drugs within 12 days prior to the first dose of lorlatinib:

    • known strong CYP3A inhibitors
    • known strong CYP3A inducers
    • known P gp substrates with a narrow therapeutic index
  • Patients with any medical or psychiatric condition, or that may, in the investigator's judgment, increase the risk of study participation or make the participant inappropriate for the study.
  • Positive pregnancy test for females of childbearing potential.
  • Breastfeeding and childbearing potential female unwilling/unable to use a highly effective contraception method for the study duration and for at least 35 days after the last dose of lorlatinib
  • Fertile male patients unwilling/unable to use a highly effective method of contraception for the duration of the study and for at least 97 days after the last dose of lorlatinib.
  • Patients participating in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
  • Patients deprived of their liberty, under protective custody or guardianship or unable to provide signed consent.
  • Patients not affiliated to the French social security system.
  • Patients opposed to the collection of their data.
  • Patients willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow-up.
  • Patients judged inapt to respond to the questions required for the study due to linguistical, psychological, social, or geographical reasons.
  • Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lorlatinib
Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously
Drug: Lorlatinib
ALK-positive NSCL treatment
Other Names:
  • PF-06463922

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: From time of Study Start up to 25 months
Time from inclusion to date of disease progression or death of any cause whichever occurs first.
From time of Study Start up to 25 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From time of Study Start up to 25 months
Time from inclusion to date of death from any cause.
From time of Study Start up to 25 months
Objective Response Rate (ORR)
Time Frame: From time of Study Start up to 24 months
proportion of patients with a Complete Response (CR) or Partial Response (PR) as a best response during the lorlatinib treatment. Responses to treatment will be defined according to investigator
From time of Study Start up to 24 months
Duration of Response (DR)
Time Frame: From time of Study Start up to 24 months
time between the first documentation of objective response and the first documentation of disease progression or death from any cause whichever occurred first, for participants with a confirmed objective response of CR or PR.
From time of Study Start up to 24 months
Intracranial Objective Response Rate (IC-ORR)
Time Frame: From time of Study Start up to 24 months
proportion of patients with intracranial objective response of complete response (CR) or partial response (PR) as a best response in the subset of patients with at least 1 intracranial lesion assessed by investigator.
From time of Study Start up to 24 months
Intracranial Time to Progression (IC-TTP)
Time Frame: From time of Study Start up to 24 months
Time from inclusion to the date of the first documentation of disease progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases.
From time of Study Start up to 24 months
Intracranial Duration of Response (IC-DR)
Time Frame: From time of Study Start up to 24 months
time from the first documentation of intracranial OR to the first documentation of intracranial progressive disease (PD) or death due to any cause, whichever occurred first for participants with a confirmed objective response of CR or PR assessed by investigator.
From time of Study Start up to 24 months
Duration of Treatment (DT)
Time Frame: From time of Study Start up to 25 months
Time between inclusion and last dose of lorlatinib.
From time of Study Start up to 25 months
Proportion of patients with extracranial progression and sites of progression
Time Frame: From time of Study Start up to 24 months
Based on Investigator's Assessment
From time of Study Start up to 24 months
Time to Treatment Failure (TTF)
Time Frame: From time of Study Start up to 24 months
Time from date of treatment initiation to date of discontinuation of treatment for any reason, including progression of disease, treatment toxicity, and death from any cause whichever occurs first.
From time of Study Start up to 24 months
Adverse Event (AE) as graded by NCI CTCAE v5)
Time Frame: From time of Study Start up to 25 months
Frequency of patients experiencing treatment-emergent AEs (TEAEs)
From time of Study Start up to 25 months
Number of Participants With Treatment-Emergent Adverse Events (AEs; Treatment-Related
Time Frame: From time of Study Start up to 25 months
Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. Treatment-related AEs were determined by investigators.
From time of Study Start up to 25 months
Proportion of patients considered observant to treatment assessed by the compliance questionnaire.
Time Frame: At the start of cycle (each cyle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and then every 3 months - as long as 48 months
Self-administered questionnaire that provides a measure of compliance
At the start of cycle (each cyle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and then every 3 months - as long as 48 months
Proportion of patients experiencing a 10-points change from baseline in total score for the EORTC QLQ-C30
Time Frame: At inclusion, At the start of Cycle (each cycle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months
evaluate Health-related Quality of life (HRQoL) of ALK- positive locally advanced or metastatic NSCLC patients treated with lorlatinib in first-line using the EORTC QLQ-C30 questionnaires
At inclusion, At the start of Cycle (each cycle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months
Proportion of patients experiencing a 10-points change from baseline in total score for the EORT QLQ-LC13.
Time Frame: At inclusion, At the start of Cycle (each cycle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months
Evaluate Health-related Quality of life (HRQoL) of ALK- positive locally advanced or metastatic NSCLC patients treated with lorlatinib in first-line using the EORTC QLQ -LC13 questionnaires
At inclusion, At the start of Cycle (each cycle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months
Patient Reported Outcome-informed CNS symptomatic toxicity:
Time Frame: At inclusion, At the start of cycle (each cycle is 28 days) Cycle1Day15, Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months
frequency, severity and/or interference with daily activities, amount, presence/absence according to PRO-CTCAE questionnaires for mood (anxious/discouraged/sad), and attention/memory items (concentration/memory).
At inclusion, At the start of cycle (each cycle is 28 days) Cycle1Day15, Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months
Proportion of patients experiencing grade III toxicities or progression and having an over- or under-exposure to lorlatinib.
Time Frame: At baseline, at start of Cycle1Day15 (each cycle is 28 days), Month 3, Month 9 and every 6 months through the end of treatment, at time of first grade III of hyperlipidaemia and CNS toxicity onset, and at progression - as long as 48 months
At each time point, a blood sample to provide plasma for determination of the plasma concentrations of lorlatinib.
At baseline, at start of Cycle1Day15 (each cycle is 28 days), Month 3, Month 9 and every 6 months through the end of treatment, at time of first grade III of hyperlipidaemia and CNS toxicity onset, and at progression - as long as 48 months
Proportion of patients experiencing each kind of identified lorlatinib resistance mechanisms
Time Frame: At baseline and at the date of first documented progression (as long as 48 months)
Plasma samples collected at baseline and end of treatment, analyzed by next-generation sequencing
At baseline and at the date of first documented progression (as long as 48 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 20, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 5, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 5, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B7461051
  • LOREA (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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