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

NCT07415005 | Recruiting Phase 2 DMC

• 2 other identifiers: 2025-1552NCI-2026-01061
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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

  Through study completion; an average of 1 year

Study Arms (2)

G1_LLT: Phase 2 Group 1 Mono Treatment with Lorlatinib

EXPERIMENTAL

All 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.

Drug: Lorlatinib

G2_LLT+LCT: Phase 2 Group 2 Combo Treatment with Lorlatinib+Local Consolidation Therapy (LCT)

EXPERIMENTAL

All 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.

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

Given Orally

Also known as: Lorbrena

G1_LLT: Phase 2 Group 1 Mono Treatment with Lorlatinib; G2_LLT+LCT: Phase 2 Group 2 Combo Treatment with Lorlatinib+Local Consolidation Therapy (LCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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 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).
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Interventions

lorlatinib

Study Officials

• Yasir Y Elamin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yasir Y Elamin, MD

CONTACT

(713) 792-3428; yyelamin@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2026
• First Posted: February 17, 2026
• Study Start: April 24, 2026
• Primary Completion (Estimated): July 22, 2028
• Study Completion (Estimated): July 22, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)