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

Official title

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

Overview

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

Interventions

• Drug Lorlatinib
  ALK-positive NSCL treatment

Primary outcome measures

• Progression-Free Survival (PFS) [Time frame: From time of Study Start up to 25 months]

Secondary outcome measures (12)

• Overall Survival (OS) [Time frame: From time of Study Start up to 25 months]
• Objective Response Rate (ORR) [Time frame: From time of Study Start up to 24 months]
• Duration of Response (DR) [Time frame: 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]
• Intracranial Time to Progression (IC-TTP) [Time frame: 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]
• Duration of Treatment (DT) [Time frame: 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]
• Time to Treatment Failure (TTF) [Time frame: 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]
• Number of Participants With Treatment-Emergent Adverse Events (AEs; Treatment-Related [Time frame: 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 31 centers

• Institut Curie — Paris
• Centre Hospitalier du Pays d AIX — Aix-en-Provence
• CH ALBI — Albi
• Chu Amiens Sud — Amiens
• Ch Avignon — Avignon
• Polyclinique Bordeaux Nord Aquitaine — Bordeaux
• Institut Bergonie — Bordeaux
• Hopital Morvan — Brest
• … and 23 more centers

Identifiers

NCT: NCT06487078 · B7461051 · LOREA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗