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

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: Recruiting
• Conditions: ALK+ Non-Small-Cell Lung Carcinoma
• Intervention / Treatment: Drug: Lorlatinib

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

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
    • Hôpital 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
    • Hopital Cochin
  • Paris, France, 75908
    • Recruiting
    • Hôpital Européen 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
    • Hopital Pontchaillou
  • Suresnes, France, 92151
    • Recruiting
    • Hopital Foch
  • TSA 50032 Toulouse, France, 31059
    • Recruiting
    • Hopital 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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from inclusion to date of death from any cause.	From time of Study Start up to 25 months
Objective Response Rate (ORR)	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 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)	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 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 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 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	Based on Investigator's Assessment	From time of Study Start up to 24 months
Time to Treatment Failure (TTF)	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)	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	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.	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	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.	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:	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.	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	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

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; lorlatinib
• Other Study ID 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