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Advanced Non-Small Cell Lung CancerPhase 2NCT07415005

Lorlatinib Plus Local Consolidation Therapy In ALK Positive Advanced Non-Small Cell Lung Cancer

A Phase 2 study testing Lorlatinib in people with Advanced Non-Small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is an open-label, multicenter, randomized phase 2 trial for patients with tyrosine kinase inhibitor-naïve ALKrearranged advanced NSCLC. Subjects are initially treated with lorlatinib for 12 weeks. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Non-Small Cell Lung Cancer
What is being tested?
Lorlatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
24 Apr 2026to 22 Jul 2030
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

  • Subjects must meet all the following criteria to be included in this study:
  • Histologically or cytologically confirmed diagnosis of stage IV NSCLC (or recurrent NSCLC not a candidate for definitive multimodality therapy)
  • Documented ALK re-arrangement as detected by: (1) FISH, (2) IHC, (3) tissue NGS, or (4) cfDNA NGS
  • Subjects can be enrolled as (a) TKI naïve or (b) after/during 12 weeks of first line lorlatinib treatment without disease progression or (c) ≤4 weeks of first line alectinib, brigatinib or ensartinib treatment without disease progression, those patients must be switched to lorlatinib.
  • Candidate for local consolidation therapy in the opinion of the treating physician.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
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  • Males or females ≥ 18 years. Because no dosing or adverse event data are currently available on the use of lorlatinib in combination with other agents in patients <18 years of age, children are excluded from this study.
  • Adequate organ function laboratory values, defined as:
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L or at least 1000/mm3 .Platelet count at least 75,000/mm3 or at least 75 x 109/L
  • Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline
  • Serum creatinine ≤ 1.5 × ULN or ≥ 45mL/minute creatinine clearance for subjects with creatinine levels > 1.5 × the institutional ULN
  • Serum total bilirubin less than or equal to ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 × ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN except for subjects with liver metastases for whom ALT and AST should be ≤ 5× ULN
  • International Normalized Ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy if PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated PTT (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulant
  • Female patients of childbearing potential must have a negative pregnancy test documented at time of screening.
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to use a highly effective method of contraception from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse The effects of lorlatinib on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
  • <!-- -->
  • Postmenopausal (no menses in greater than or equal to 12 consecutive months).
  • History of hysterectomy or bilateral salpingo-oophorectomy.
  • Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
  • History of bilateral tubal ligation or another surgical sterilization procedure.
  • Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide.
  • Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
  • Agree to completely abstain from heterosexual intercourse
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of lorlatinib administration.
  • Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of
  • ≤450 milliseconds (msec) in males or ≤470 msec in females.
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Subjects who meet any of the following criteria will be excluded from this study:
  • Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who have had at least 2 years elapsed since the completion of radical treatment and the adjuvant therapy, if any, of the other primary malignancy.
  • Previously received any prior TKI, including ALK-targeted TKIs. Note: on-going first line alectinib, brigatinib, lorlatinib and ensartinib use as specified in the Inclusion criteria is allowed.
  • Previously received more than 1 cycle of chemotherapy +/-immunotherapy for locally advanced or metastatic disease.
  • Symptomatic CNS metastasis. Asymptomatic CNS disease requiring increasing dose of corticosteroids within 7 days prior to study enrollment is also not permitted.
  • Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging).
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  • Patients with leptomeningeal disease and without cord compression are allowed.
  • The presence of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis at screening.
  • Have a known or suspected hypersensitivity to lorlatinib or its excipients.
  • Have malabsorption syndrome or other gastrointestinal (GI) illness or condition that could affect oral absorption of the study drug.
  • Have uncontrolled hypertension. Patients with hypertension as defined by current standard of practice should be under treatment on study entry to control blood pressure.
  • Received radiation therapy within 14 days before randomization except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
  • Had major surgery within 30 days of enrollment. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
  • Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to the following: a) Myocardial infarction within 6 months before enrollment. b) Unstable angina within 6 months before enrollment. c) New York Heart Association Class III or IV heart failure within 6 months before enrollment. d) History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician. e) Any history of clinically significant ventricular arrhythmia.
  • Had a cerebrovascular accident within 6 months before first dose of study drug.
  • Have an ongoing or active infection, including the requirement for intravenous antibiotics.
  • Subjects should not receive other anti-cancer agents (e.g., chemotherapy, immunotherapy, biologic therapy, and/or hormone therapy other than for replacement or appetite stimulant) while on treatment in this study.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lorlatinib.
  • Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.
  • Pregnant women are excluded from this study because lorlatinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lorlatinib, breastfeeding should be discontinued if the mother is treated with lorlatinib. These potential risks may also apply to other agents used in this study -

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yasir Y Elamin, MD contact

(713) 792-3428

yyelamin@mdanderson.org

United States1 site, 1 recruiting

  • The University of Texas M. D. Anderson Cancer Center

    Houston, Texas, 77030

    Yasir Y Elamin, MD, 713-792-3428, yyelamin@mdanderson.org

    Yasir Y Elamin, MD

    Recruiting

Other trials in United States

About this study

This is an open-label, multicenter, randomized phase 2 trial for patients with tyrosine kinase inhibitor-naïve ALKrearranged advanced NSCLC. Subjects are initially treated with lorlatinib for 12 weeks.

Read the detailed description

Primary Objective:

  1. To compare the PFS of ALK+ NSCLC patients treated with lorlatinib to those treated with lorlatinib and local consolidation therapy (LCT)

Secondary Objectives:

  1. To assess the safety and tolerability of lorlatinib and LCT.
  2. To increase trial enrollment in underserved population
  3. To determine overall survival (OS) in patients treated with single agent lorlatinib vs lorlatinib plus LCT.
  4. To assess the time to progression of non-LCT lesions in the lorlatinib plus LCT arm.

Exploratory Biomarkers Objectives:

  1. To determine the utility of pre-treatment, pre-LCT, and post-LCT circulating free tumor DNA (cfDNA) as potential prognostic and predictive biomarkers.
  2. To evaluate potential impact of LCT on mechanisms of lorlatinib resistance with molecular analysis of postprogression biopsies.
Being tested
Lorlatinib

What participants receive

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

  • LorlatinibDrug

    Also called Lorbrena

    Given Orally

Study groups in NCT07415005
Study groupRoleWhat they receive
G1_LLT: Phase 2 Group 1 Mono Treatment with LorlatinibExperimentalAll patients will receive lorlatinib orally daily for an induction period of 12 weeks prior to randomization, for patients treated for another first line ALK TKI for 4 weeks or less and switched to lorlatinib, they will receive lorlatinib up to a total time of 12 weeks on an ALK TKI pre-randomization.
Receives: Drug: Lorlatinib
G2_LLT+LCT: Phase 2 Group 2 Combo Treatment with Lorlatinib+Local Consolidation Therapy (LCT)ExperimentalAll patients will receive lorlatinib orally daily for an induction period of 12 weeks prior to randomization, for patients treated for another first line ALK TKI for 4 weeks or less and switched to lorlatinib, they will receive lorlatinib up to a total time of 12 weeks on an ALK TKI pre-randomization.
Receives: Drug: Lorlatinib

What is being measured

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

  1. Safety and Adverse Events (AEs)

    Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 6.0

    Measured: Through study completion; an average of 1 year

Timeline

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

  1. First posted17 Feb 2026
  2. Study start24 Apr 2026
  3. Primary completion22 Jul 2028 (estimated)
  4. Study completion22 Jul 2030 (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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07415005
Sponsor's protocol ID
2025-1552
Other IDs
NCI-2026-01061
Status last verified
Oct 2026
First submitted
13 Feb 2026
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
Yes
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 Advanced Non-Small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

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 35 inclusion and 20 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: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Contact Yasir Y Elamin, MD ((713) 792-3428, yyelamin@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year). 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 NCT07415005.

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 13 Oct 2026.

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