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Non Small Cell Lung Cancer MetastaticPhase 2NCT04621188

Lorlatinib After Failure of First-line TKI in Patients With Advanced ROS1-positive NSCLC (ALBATROS)

A Phase 2 study testing Lorlatinib in people with Non Small Cell Lung Cancer Metastatic, run by Intergroupe Francophone de Cancerologie Thoracique at 34 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

ROS1 rearrangements are present in 1-2% of NSCLC cases and define a distinct molecular subgroup. Like ALK (anaplastic lymphoma kinase) rearrangements in NSCLC, ROS1 fusions confer sensitivity to the inhibitor crizotinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer Metastatic
What is being tested?
Lorlatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
34 sitesFrance
Study dates
19 Mar 2021to Feb 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed Written Informed Consent: Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing
  • Patients with histologically or cytologically confirmed diagnosis of locally advanced not eligible to a local treatment or metastatic NSCLC (Stage IIIB, IIIC or IV accordingly to 8th classification TNM, UICC 2015) that carries an ROS1 rearrangement, as determined by the molecular biology platform of the investigator by FISH assay or by Immunohistochemistry (IHC), or Next Generation Sequencing (NGS) or RNA sequencing approach.
  • Disease Status Requirements: Disease progression meeting RECISTv1.1 after one prior line of treatment with crizotinib or entrectinib (+ one line of chemotherapy with or without immunotherapy before TKI treatment).
  • Note: patient with disease progression after treatment with another ROS1-TKI may still be eligible upon discussion with IFCT.
  • Tumor Requirements: All Patients must have at least one measurable target lesion according to RECIST v1.1. The radiological assessment has to be done within the timelines indicated. In addition, patients with asymptomatic and neurologically stable CNS metastases (including patients controlled with stable or decreasing steroid use within the last week prior to study entry) will be eligible. The brain metastases may be newly diagnosed after disease progression with crizotinib or entrectinib or be present as progressive disease after surgery, whole brain radiotherapy or stereotactic radiosurgery (see Exclusion Criterion for the lapsed time period required between the end of radiotherapy and study entry). Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) will be eligible if the LM/CM is visualized on MRI or if documented baseline cerebral spinal fluid (CSF) positive cytology is available and asymptomatic and neurologically stable (including patients controlled with stable or decreasing steroid use within the last week prior to study entry).
  • Tumor Sample Requirement: Tumour biopsy sampling on fresh tissue (FFPE blocks required) obtained after progression on crizotinib or entrectinib. Tumour biopsy should be exploitable for molecular analysis. If the tumour biopsy is not exploitable, the inclusion will be allowed if two blood samples are provided for tumoral cfDNA analysis. The Sponsor will monitor a posteriori the exploitability of provided tumour biopsies and will investigate the impossibility to perform or repeat tissue tumor sampling.
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  • Age ≥18 years.
  • Life expectancy of at least 12 weeks, in the opinion of the Investigator.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
  • Adequate Bone Marrow Function, including: Absolute Neutrophil Count (ANC) ≥1.5 x 109/L; Platelets ≥100 x 109/L; Hemoglobin ≥9 g/dL.
  • Adequate Pancreatic Function, including: Serum lipase ≤1.5 x ULN.
  • Adequate Renal Function, including: Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥45 mL/min as calculated using the method standard for the institution.
  • Adequate Liver Function, including: Total serum bilirubin ≤1.5 x ULN; Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN; ≤5.0 x ULN if there is liver metastases involvement.
  • Participants must have recovered from treatment toxicities to CTCAE Grade ≤ 1 (for participants who have developed interstitial lung disease [ILD], they must have fully recovered) except for AEs that in the investigator' judgment do not constitute a safety risk for the patient.
  • Participants must have recovered from effects of any major surgery, or significant traumatic injury, at least 35 days before the first dose of lorlatinib
  • For all females of childbearing potential, a negative pregnancy test must be obtained within the screening period. A patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active. Additionally, all females of childbearing potential must provide an agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 90 days after the last dose of study drug.
  • For men: agreement to remain abstinent or use an effective method of contraception (e.g., condom) during the treatment period and for at least 14 weeks after the last dose of study drug and agreement to refrain from donating sperm during this same period.
  • Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
  • Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedure.
  • Participant has national health insurance coverage.
  • Washout period: if previous progression on ROS1-TKI: 7 days from last dose of the drug. The washout period may be shortened to 2 days at investigator discretion.

Who cannot join

  • Participants with disease progression on front-line treatment with TKI i.e. crizotinib or entrectinib limited to CNS or one non-CNS site (oligo-metastasis) and eligible to a local ablative treatment (surgery or stereotaxic radiotherapy).
  • Histological transformation with neuro-endocrine differentiation.
  • Spinal cord compression is excluded unless the patient demonstrates good pain control attained through therapy and there is stabilization or recovery of neurological function for the 4 weeks prior to study entry.
  • Patients with symptomatic and neurologically instable CNS metastases or leptomeningeal metastasis (including patients that require increasing doses of steroids within one week prior to Day 0 of screening phase and during the screening phase to manage CNS symptoms).
  • Major surgery within 35 days of study entry. Minor surgical procedures (eg, port insertion, mediastinoscopy, surgical procedure for re-sampling) are not excluded, but sufficient time at investigator discretion should have passed for wound healing.
  • Radiation therapy within 2 weeks of study entry (except palliative to relieve bone pain). Palliative radiation (≤15 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
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  • 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-CTLA-4.
  • 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 <3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ 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 <50 bpm (unless patient is otherwise healthy such as long-distance runners, athletic patients etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome.
  • Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (eg, uncontrolled hyperglycemia, current gallstone disease, alcoholism [more than 4 drinks on any day or 14 drinks per week where 1 drink is defined as the alcoholic beverage containing approximately 14 grams of pure alcohol, eg, 12 fl oz/360 mL regular beer or 5 fl oz/150 mL of wine] in the last month.
  • History of bilateral or Grade 3 or 4 interstitial fibrosis or diffuse interstitial lung disease. Patients with history of prior radiation pneumonitis are not excluded.
  • Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, DCIS of the breast or localized and presumed cured prostate cancer) within the last 3 years.
  • Active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease or previous gastric resection or lap band.
  • Current use or anticipated need for food or drugs prohibited (see chapter 7.9 for details).
  • Patients presenting with abnormal Left Ventricular Ejection Fraction (LVEF) by echocardiogram or Multi-Gated Acquisition Scan (MUGA) according to institutional lower limits.
  • Breastfeeding female patients (including patients who intend to interrupt breastfeeding).
  • Liver disease characterized by: ALT or AST level > 3 the upper normal limit (UNL) (≥ 5 x UNL for patients with liver metastases) confirmed on 2 consecutive measures OR impaired excretory function (e.g.. hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease e.g.: coagulopathy, Hepatic encephalopathy, hypoalbuminemia, ascites and bleeding from esophageal varices OR Acute viral or autoimmune or other types of hepatitis.

Trial locations and contacts

34 sites in 1 country.

34 sites in 1 country

France34 sites

  • Centre Hospitalier du Pays d'Aix

    Aix-en-Provence, 13616

  • Centre Paul Papin

    Angers, 49055

  • Angers - CHU

    Angers

  • Annecy - CH

    Annecy

  • Antony - Hôpital privé

    Antony

  • Avignon - CH

    Avignon

  • Centre Hospitalier de la Côte Basque

    Bayonne, 64100

  • Bordeaux - CHU

    Bordeaux

  • Bordeaux - Institut Bergonie

    Bordeaux

  • Bordeaux - Polyclinique

    Bordeaux

  • AP-HP Hôpital Ambroise Paré

    Boulogne, 92104

  • Caen - CHU Côte de Nacre

    Caen, 14000

  • Chauny - CH

    Chauny

  • Cholet - CH

    Cholet

  • Clermont-Ferrand - CHU

    Clermont-Ferrand

  • Colmar - CH

    Colmar

  • Centre Hospitalier Intercommunal de Créteil

    Créteil, 94000

  • Dijon - CRLCC

    Dijon

  • CHRU Grenoble

    Grenoble

  • Centre Hospitalier - Pneumologie

    Le Mans, 72000

  • Hôpital Calmette

    Lille, 59037

  • Centre Léon Bérard

    Lyon, 69373

  • Institut Paoli Calmettes

    Marseille, 13273

  • GRH Mulhouse Sud-Alsace

    Mulhouse

  • AP-HP Hôpital Cochin

    Paris, 75014

  • AP-HP Hopital Tenon - Pneumologie

    Paris, 75020

  • Lyon - URCOT

    Pierre-Bénite

  • Rouen - CHU

    Rouen

  • Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67091

  • Hôpital Foch

    Suresnes, 92151

  • CHU Toulouse - Pneumologie

    Toulouse

  • CHU Bretonneau

    Tours, 37044

  • Valenciennes - Clinique

    Valenciennes

  • Vandoeuvre-lès-Nancy - CHU

    Vandœuvre-lès-Nancy

Other trials in France

About this study

Official title: A Phase II Single-group Assignment, Multicenter Study of Efficacy and Safety of Lorlatinib Monotherapy After Failure of First-line Tyrosine Kinase Inhibitor in Patients With Advanced ROS1-positive Non-small Cell Lung Cancer (ALBATROS)

ROS1 rearrangements are present in 1-2% of NSCLC cases and define a distinct molecular subgroup. Like ALK (anaplastic lymphoma kinase) rearrangements in NSCLC, ROS1 fusions confer sensitivity to the inhibitor crizotinib. Crizotinib, which is a tyrosine kinase inhibitor (TKI), has been shown to be effective in tumors in several retrospective studies.

Recently the FDA approved entrectinib for the treatment of patients with ROS1-positive metastatic NSCLC. This indication is based on the results of pooled data from several trials. Together, these studies demonstrate the efficacy for entrectinib across a variety of solid tumor types including NSCLC with ROS1 fusion.

Read more

However, despite the efficacy of crizotinib or entrectinib in ROS1-positive NSCLC, patients will develop resistance to these tyrosine kinase inhibitors.

Lorlatinib is a new and potent ROS1 / ALK inhibitor optimized to penetrate the blood-brain barrier. A recent study has investigated the activity of lorlatinib against the crizotinib-resistant ROS1G2032R mutation. In this situation, lorlatinib effectively inhibited the catalytic activity of recombinant ROS1G2032R resulting in an antiproliferative response. Because of its potency as an ROS1 inhibitor and its ability to suppress the resistant ROS1 mutations, lorlatinib could be a treatment of choice in ROS1-positive NSCLC.

Being tested
Lorlatinib
Keywords
IFCT, ALBATROS, NSCLC, ROS1-positive, monotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LorlatinibDrug

    100 mg once daily

Study groups in NCT04621188
Study groupRoleWhat they receive
LorlatinibExperimental100 mg once daily
Receives: Drug: Lorlatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) at 8 weeks by investigators

    ORR is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) as per RECIST v1.1 criteria.

    Measured: 8 weeks

Secondary outcomes (10)

  1. Overall Response Rate (ORR) at 8 weeks by Independent Reviewer Committee (IRC)

    Percentage of subjects with a confirmed at 16 weeks complete response (CR) or partial response (PR) as per RECIST v1.1 criteria.

    Measured: 8 weeks

  2. Progression Free Survival (PFS)

    Time between the date of first dose of study drug and the first date of documented disease progression (according to RECIST v1.1) or death (from any cause)

    Measured: Up to 24 months

  3. Time to progression (TTP)

    Time from the date of first dose of study drug to the earliest date of disease progression (according to RECIST v1.1.)

    Measured: Up to 24 months

  4. Disease control rate (DCR) at 8 weeks weeks)

    Proportion of patients have achieved a confirmed best overall response of CR, PR or SD (Stable Disease) (according to RECIST v1.1.)

    Measured: 8 weeks

  5. Duration of response (DOR) first documented response (CR or PR) to the earliest date of disease progression, or death due to any cause.

    Time from the date of the first documented response (CR or PR) to the earliest date of disease progression or death due to any cause.

    Measured: Up to 24 months

  6. Overall survival (OS) months

    Time from the date of first dose of study drug to the date of death due to any cause

    Measured: 12 months and 24 months

  7. Central Nervous System (CNS) Objective response rate (C-ORR)

    ORR estimated in patients with measurable CNS metastases at baseline.

    Measured: Up to 24 months

  8. CNS duration of response (C-DOR) measurable CNS metastases at baseline.

    DOR estimated in patients with measurable CNS metastases at baseline.

    Measured: Up to 24 months

  9. Time to CNS progression

    In patients without brain metastases baseline.

    Measured: Up to 24 months

  10. Change from baseline of EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)

    At all scheduled time points

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2020
  2. Study start19 Mar 2021
  3. Primary completion26 Feb 2025
  4. Study completionFeb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04621188
Sponsor's protocol ID
IFCT-2003
Other IDs
2024-512028-12-00
Status last verified
Sep 2025
First submitted
4 Nov 2020
Last updated
24 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lorlatinib in people with Non Small Cell Lung Cancer Metastatic, run by Intergroupe Francophone de Cancerologie Thoracique at 34 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) at 8 weeks by investigators (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04621188.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2025.

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